Surfactant Protein A Levels Research Articles

Presence of surfactant proteins in the uteri and placentae of pregnant mares.

Immunohistochemical investigations of the expression of surfactant protein A (SP-A) and surfactant protein D (SP-D) in the uterine and placental tissues of 13 pregnant mares were performed using anti-horse monoclonal primary antibodies. Strong positive reactions for both SP-A and SP-D were observed in the trophoblasts in the microcotyledons of the placentae at 182 to 314 days of gestation; in uterine glandular epithelial cells, faint-to-weak reactions were observed during gestation. This study describes, for the first time, the changes in the SP-A and SP-D expression levels in the endometrium of mares during gestation; the SP-A and SP-D expression levels increased after the second trimester of gestation.

Serum SP-A and KL-6 levels can predict the improvement and deterioration of patients with interstitial pneumonia with autoimmune features

BackgroundSome patients with interstitial pneumonia with autoimmune features (IPAF) showed a progressive course despite therapy. This study aimed to evaluate whether serial changes in the serum levels of surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) can predict disease progression.MethodsSixty-four patients with IPAF and 41 patients with non-fibrotic lung disease (non-FLD) were examined. Based on long-term changes in lung function, 36 IPAF patients who were followed up for more than 3 months were divided into a progressive group (n = 9), an improvement group (n = 13), and a stable group (n = 14). Serum KL-6 and SP-A levels were measured. The sensitivity, specificity, cut-off value, and area under the curve (AUC) value for each of the indices were determined using receiver operating characteristic (ROC) curve analysis. The expression differences in these biomarkers and their correlation with disease severity were analyzed.ResultsCompared with non-FLD patients, serum SP-A and KL-6 levels in IPAF patients were increased significantly [SP-A: (p < 0.001); KL-6: (p < 0.001)] and negatively correlated with DLCO (SP-A: rS = − 0.323, p = 0.018; KL-6: rS = − 0.348, p = 0.0011). In patients with progressive disease, the posttreatment serum SP-A and KL-6 levels were increased significantly compared with pretreatment levels [SP-A: (p = 0.021); KL-6: (p = 0.008)]. In patients showing improvement, the levels were decreased significantly [SP-A (p = 0.007) and KL-6 (p = 0.002)]. Changes in serum biomarkers (Delta SP-A and Delta KL-6) were significantly negatively correlated with changes in lung function (Delta FVC, Delta DLCO and Delta FEV1) (rS = 0.482, p < 0.05). A significant positive correlation was found between Delta SP-A and Delta KL-6 (rS = 0.482, p < 0.001).ConclusionsSerum SP-A and KL-6 offer high sensitivity and specificity for the diagnosis of IPAF. The decrease in serum SP-A and/or KL-6 levels in patients with IPAF is related to the improvement in pulmonary function. SP-A and KL-6 may be important biomarkers for predicting disease progression in patients with IPAF.

Emodin protects against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway.

Objective: Our aim was to investigate the effect of emodin on intestinal and lung injury induced by acute intestinal injury in rats and explore potential molecular mechanisms.Methods: Healthy male Sprague–Dawley (SD) rats were randomly divided into five groups (n=10, each group): normal group; saline group; acute intestinal injury model group; model + emodin group; model+NF-κB inhibitor pynolidine dithiocarbamate (PDTC) group. Histopathological changes in intestine/lung tissues were observed by Hematoxylin and Eosin (H&E) and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) staining. Serum IKBα, p-IKBα, surfactant protein-A (SP-A) and toll-like receptor 4 (TLR4) levels were examined using enzyme-linked immunosorbent assay (ELISA). RT-qPCR was performed to detect the mRNA expression levels of IKBα, SP-A and TLR4 in intestine/lung tissues. Furthermore, the protein expression levels of IKBα, p-IKBα, SP-A and TLR4 were detected by Western blot.Results: The pathological injury of intestinal/lung tissues was remarkedly ameliorated in models treated with emodin and PDTC. Furthermore, the intestinal/lung injury scores were significantly decreased after emodin or PDTC treatment. TUNEL results showed that both emodin and PDTC treatment distinctly attenuated the apoptosis of intestine/lung tissues induced by acute intestinal injury. At the mRNA level, emodin significantly increased the expression levels of SP-A and decreased the expression levels of IKBα and TLR4 in intestine/lung tissues. According to ELISA and Western blot, emodin remarkedly inhibited the expression of p-IKBα protein and elevated the expression of SP-A and TLR4 in serum and intestine/lung tissues induced by acute intestinal injury.Conclusion: Our findings suggested that emodin could protect against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway.

Serum Levels of Collectins Are Sustained During Pregnancy: Surfactant Protein D Levels Are Dysregulated Prior to Missed Abortion.

About 15% of pregnant women undergo missed abortion (MA), wherein women do not experience cramping and vaginal bleeding. Dysregulation of the immune molecules and steroid hormones contribute to early pregnancy loss. Collectins- surfactant protein A (SP-A), surfactant protein D (SP-D), and mannose-binding lectin (MBL) are a group of innate immune molecules regulated by the steroid hormones. Reduced levels of SP-A and SP-D during the early gestation exhibited a significant association with the severe early onset preeclampsia. In order to determine the serum profile of collectins throughout the normal pregnancy and explore their predictive potential during the 8-12weeks of gestation for MA, we examined a prospective cohort of pregnant women (n = 221). The serum levels of SP-A and SP-D were significantly downregulated in the normal pregnant women in all the three trimesters (n = 30) compared with the non-pregnant women (n = 20) and were not significantly different across the three trimesters. Fourteen of the women from the cohort underwent MA during the 14-20weeks of gestation and exhibited a significant downregulation in the serum levels of SP-D during 8-12weeks of gestation. A significant inhibition of the HTR-8/SVneo cell proliferation and migration in the presence of a recombinant fragment of human SP-D suggested the relevance of SP-D in placental development. We report here that the serum levels of SP-A, SP-D, and MBL are consistently maintained during pregnancy in the Indian cohort. Dysregulated serum levels of SP-D and P4/E2 ratio during the early first trimester may predict occurrence of MA.

Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages

Pneumonia is the leading cause of hospitalization worldwide. Besides viruses, bacterial co-infections dramatically exacerbate infection. In general, surfactant protein-A (SP-A) represents a first line of immune defense. In this study, we analyzed whether influenza A virus (IAV) and/or Staphylococcus aureus (S. aureus) infections affect SP-A expression. To closely reflect the situation in the lung, we used a human alveolus-on-a-chip model and a murine pneumonia model. Our results show that S. aureus can reduce extracellular levels of SP-A, most likely attributed to bacterial proteases. Mono-epithelial cell culture experiments reveal that the expression of SP-A is not directly affected by IAV or S. aureus. Yet, the mRNA expression of SP-A is strongly down-regulated by TNF-α, which is highly produced by professional phagocytes in response to bacterial infection. By using the human alveolus-on-a-chip model, we show that the down-regulation of SP-A is strongly dependent on macrophages. In a murine model of pneumonia, we can confirm that S. aureus decreases SP-A levels in vivo. These findings indicate that (I) complex interactions of epithelial and immune cells induce down-regulation of SP-A expression and (II) bacterial mono- and super-infections reduce SP-A expression in the lung, which might contribute to a severe outcome of bacterial pneumonia.

Clinical significance of thyroid hormone and antibodies in patients with idiopathic interstitial pneumonia.

BackgroundHypothyroidism was recently reported to be common and to predict mortality in patients with idiopathic pulmonary fibrosis (IPF). In addition, a high prevalence of hypothyroidism was shown in patients with idiopathic pleuroparenchymal fibroelastosis. However, in idiopathic interstitial pneumonia (IIP), a clinical significance of thyroid function has not been clarified in detail. The goal of this study was to investigate the clinical significance of thyroid function and the presence of thyroid antibodies in IIP.MethodsWe have reviewed IIP patients, and analyzed the positivity of thyroid antibodies at first. Next, the relationship of clinical characteristics with thyroid function and the positivity of thyroid antibodies was analyzed. Lastly, the positivity of thyroid antibodies and other autoantibodies was evaluated.ResultsIn IIP patients, thyroglobulin and thyroid peroxidase antibodies were positive in 17 and 16%, respectively, and 22% of patients had either or both antibodies. Subclinical and/or overt hypothyroidism was confirmed in 7% of IIP patients. The free thyrotropin level had a significant positive correlation with vital capacity and a significant negative correlation with the C-reactive protein and surfactant protein-A levels, and erythrocyte sedimentation ratio (ESR). In addition, autoantibodies suggestive of connective tissue diseases (CTDs) were positive in more than two thirds of IIP patients with the thyroid antibody, and the positive rate of antinuclear and proteinase-3 anti-neutrophil cytoplasmic antibodies was significantly higher in IIP patients with thyroid antibodies than those without the antibodies.ConclusionsAlthough thyroid dysfunction is not frequent, thyroid hormones and thyroid antibodies are possibly involved in the pathogenesis of IIP and their evaluation may be clinically useful to identify the clinical phenotype of IIP with autoimmune features.

Surfactant protein A expression and distribution in human lung samples from smokers with or without chronic obstructive pulmonary disease in China.

Cigarette smoking is considered the main risk factor for chronic obstructive pulmonary disease (COPD), although the mechanism remains unknown. surfactant protein A (SP-A) is thought to protect the lung from smoking-induced damage, but related studies performed in China are scarce. The aim of the study is to assess alterations of SP-A expression and distribution in lung samples from Chinese smokers with or without COPD.This cross-sectional study assessed 45 men in Wuhan Tongji Hospital after lobectomy for lung cancer in June 2010 to September 2010. Peripheral lung specimens were collected from control nonsmokers without airflow obstruction (nonsmoking group, n = 15), smokers without airflow obstruction (smoking group, n = 15), and patients with COPD (COPD group, n = 15). SP-A expression levels in lung tissue samples and its distribution in lung cells, type II pneumocytes (PNII), and alveolar macrophages (MACR) were determined by immunoblotting and immunohistochemistry.SP-A levels were significantly decreased in the COPD group (1.00 ± 0.25) compared with the smoking (2.31 ± 0.64) and nonsmoking (8.03 ± 2.80) groups; the smoking group also showed significantly reduced levels compared with the nonsmoking group (P < .05). PNII expressing SP-A were less abundant in the COPD group (39.3% ± 7.1%) compared with the smoking group (76.2% ± 29.8%), whereas SP-A+ MACR were more abundant (92.4% ± 7.1% vs 68.5% ± 20.2%) (all P < .05). Among the 30 smokers, forced expiratory volume in one second (% predicted) was positively correlated with SP-A levels (r = 0.739) and the rate of SP-A+ PNII (r = 0.811), and negatively correlated with the rate of SP-A+ MACR (r = −0.758) (all P < .05).Changes in SP-A expression and distribution in lung tissues may be involved in COPD pathogenesis in smokers.

Mechanism of IL-8-induced acute lung injury through pulmonary surfactant proteins A and B.

This study explored how interleukin-8 (IL-8) causes acute lung injury (ALI) through pulmonary surfactant protein A (SP-A) and surfactant protein B (SP-B). Serum was collected from 53 ALI patients and further 56 healthy subjects who underwent physical examination. The IL-8, SP-A, and SP-B levels were determined using enzyme-linked immunosorbent assay (ELISA). An ALI model was constructed using lipopolysaccharide (LSP)-induced normal A549 cells. siRNA was employed to interfere with the expression of IL-8, SP-A and SP-B. Western blot analysis was carried out to determine the protein levels, and MTT assay to determine the cell activity. In addition, co-immunoprecipitation (Co-IP) assay was used to verify the interaction between IL-8, SP-A and SP-B. ALI patients showed high expression of serum IL-8, and low expression of SP-A and SP-B, and IL-8 was negatively correlated with SP-A and SP-B, respectively. LSP-induced normal A549 cells showed increased expression of IL-8 and decreased expression of SP-A and SP-B. Silencing IL-8 led to increased expression levels of SP-A, SP-B and Bcl2, decreased expression levels of caspase-9, caspase-3, Bax, TNF-α, IL-17 and IL-1β, reduced cell apoptosis rate, and enhanced cell viability. Silencing SP-A and SP-B resulted in increased expression of IL-8, caspase-9, caspase-3, Bax, TNF-α, IL-17 and IL-1β, and decreased expression of Bcl2. Co-IP assay revealed that IL-8 could interact with SP-A and SP-B, respectively. IL-8 induces apoptosis by inhibiting SP-A and SP-B, and intensifies cellular inflammatory reaction, leading eventually to ALI.

Evaluation of the Diagnostic Efficacies of Serological Markers KL-6, SP-A, SP-D, CCL2, and CXCL13 in Idiopathic Interstitial Pneumonia

Background: The objective of this study was to evaluate the diagnostic value of serological markers Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), SP-D, chemokine ligand 2 (CCL2), and chemokine 13 (CXCL13) in idiopathic interstitial pneumonia (IIP). Methods: Patients with IIP aged 18–80 years from the First Affiliated Hospital of Guangzhou Medical University were enrolled in this retrospective case-control study. Data on the general patient characteristics, laboratory test results, chest high-resolution CT, and pulmonary function test results were collected. The diagnosis of idiopathic pulmonary fibrosis (IPF) was based on the international practice guidelines for the diagnosis and treatment of IPF, a collaborative effort published by the American Thoracic Society (ATS)/European Respiratory Association (ERS), Japanese Respiratory Society, and Latin American Thoracic Society. The diagnostic criteria of non-IPF (N-IPF) followed the consensus classification of the IIPs, which was jointly issued by the ATS and ERS in 2002. The diagnosis of interstitial pneumonia with autoimmune features (IPAF) was based on the official research statement on IPAF, which was jointly issued by the ATS and ERS in 2015. Serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 were measured. The differences in the expression of these biomarkers and their correlation with the severity of the disease were analyzed. The sensitivity, specificity, cutoff value, and area under the curve (AUC) value for each of the indices were determined using the receiver operating characteristic (ROC) curve analysis. Findings: Between September 2015 and October 2017, 69 patients with IIP. Of these patients, 19 had IPF, 23 had N-IPF, and 27 had IPAF. We also enrolled 20 age- and gender-matched patients with pneumonia and 15 uninfected individuals as normal control. The serum levels of KL-6, SP-A, ­SP-D, CCL2, and CXCL13 were significantly higher in patients with IIP than in patients with pneumonia and the normal controls. The detection of these markers was found to have better diagnostic efficacy in patients with IIP than in those with pneumonia. Of these markers above, KL-6 had the highest diagnostic value (AUC 0.96, 95% CI 0.93–0.99). Based on a logistics regression analysis, the combination of KL-6, CCL2, and CXCL13 had an improved diagnostic efficacy for IIP. In patients with IIP, the serum levels of KL-6, SP-A, CCL2, and CXCL13 all showed a significant negative correlation with the diffusing capacity of the lungs for carbon monoxide (DLCO; r = –0.36, –0.37, –0.36, –0.30, respectively; all p < 0.05). Although their expression levels along with that of SP-D were elevated in patients with IPF, N-IPF, and IPAF, it was difficult to distinguish between these 3 conditions by detecting the 5 serum biomarkers together. Our findings indicate that the serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 are notably elevated in patients with IIP and show significant correlation with the severity of interstitial lung lesions. Additionally, we further explore the diagnostic efficacy of 5 biomarkers in different types of IIP. It is the first time that the level of serum marker CXCL13 of N-IPF and IPAF patients was higher than IPF patients, which further enriched the study on serum markers for IIPs. Between September 2015 and October 2017, 69 patients with IIP. Of these patients, 19 had IPF, 23 had N-IPF, and 27 had IPAF. We also enrolled 20 age- and gender-matched patients with pneumonia and 15 uninfected individuals as normal control. The serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 were significantly higher in patients with IIP than in patients with pneumonia and the normal controls. Of these markers above, KL-6 had the highest diagnostic value (AUC 0.96, 95% CI 0.93–0.99). Based on a logistics regression analysis, the combination of KL-6, CCL2, and CXCL13 had an improved diagnostic efficacy for IIP. In patients with IIP, the serum levels of KL-6, SP-A, CCL2, and CXCL13 all showed a significant negative correlation with the DLCO (r = –0.36, –0.37, –0.36, –0.30, respectively; all p < 0.05). Our findings indicate that the serum levels of KL-6, ­SP-A, SP-D, CCL2, and CXCL13 are notably elevated in patients with IIP and show significant correlation with the severity of interstitial lung lesions. Additionally, we further explore the diagnostic efficacy of 5 biomarkers in different types of IIP. It is the first time that the level of serum marker CXCL13 of N-IPF and IPAF patients was higher than IPF patients, which further enrich the study on serum markers in IIPs. Interpretation: Although the combined detection of KL-6, CCL3, and CXCL13 significantly improves the diagnosis of IIP, detection of all the 5 markers together is unable to distinguish between IPF, N-IPF, and IPAF.

The role of surfactant protein-A in sinusitis.

Surfactant protein-A (SP-A) is a collectin protein expressed in airway epithelia that is critical in the modulation of both innate and adaptive immunity against inhaled pathogens. In this review, we highlight associations of altered SP-A function in asthma and chronic rhinosinusitis, and its potential role as a targeted therapy for sinusitis. SP-A has been shown to bind and opsonize inhaled pathogens, thereby clearing bacteria through phagocytosis. We have recently identified that SP-A levels are increased in response to Pseudomonas aeruginosa, a common bacterial pathogen in chronic rhinosinusitis. Moreover, SP-A has also been shown to modulate epithelial inflammatory mediators and play a role in eosinophil-mediated airway disease. The development of a transgenic murine model expressing human genetic variants of SP-A2 have suggested that the human surfactant protein-A2 223K variant significantly increases eosinophil degranulation, suggesting a genotype-phenotype correlation in human airway disease. SP-A is important in both the innate and adaptive host defense mechanisms in the upper and lower airways. Although research in this field in sinusitis is nascent, initial work suggests that aberrant SP-A regulation may be one etiologic factor in the development of bacterial and eosinophilic-associated sinusitis.

Particles in exhaled air (PExA): non-invasive phenotyping of small airways disease in adult asthma

Rationale: Asthma is often characterised by inflammation, damage and dysfunction of the small airways, but no standardised biomarkers are available. Objectives: Using a novel approach—particles in exhaled air (PExA)—we sought to (a) sample and analyse abundant protein biomarkers: surfactant protein A (SPA) and albumin in adult asthmatic and healthy patients and (b) relate protein concentrations with physiological markers using phenotyping. Methods: 83 adult asthmatics and 21 healthy volunteers were recruited from a discovery cohort in Leicester, UK, and 32 adult asthmatics as replication cohort from Sweden. Markers of airways closure/small airways dysfunction were evaluated using forced vital capacity, impulse oscillometry and multiple breath washout. SPA/albumin from PEx (PExA sample) were analysed using ELISA and corrected for acquired particle mass. Topological data analysis (TDA) was applied to small airway physiology and PExA protein data to identify phenotypes. Results: PExA manoeuvres were feasible, including severe asthmatic subjects. TDA identified a clinically important phenotype of asthmatic patients with multiple physiological markers of peripheral airway dysfunction, and significantly lower levels of both SPA and albumin. Conclusion: We report that the PExA method is feasible across the spectrum of asthma severity and could be used to identify small airway disease phenotypes.

Gender and Smoking Correlations of Surfactant Lipids and Proteins in the Saliva of Dental Patients.

We sought to determine the effects of smoking on surfactant lipids and proteins in saliva. Levels of sphingomyelin (Sph) phosphatidylcholine (PC) and lyso-PC (LPC) were determined by thin layer chromatography. Levels of surfactant protein A (SP-A) were determined by western analysis using antibodies specific for SP-A. Significance of the results was determined by the student′s t-test. The LPC/PC ratio had a tendency to be much higher in smokers compared to nonsmokers. LPC levels were significantly higher in females smokers compared to male smokers. Additionally, levels of SP-A were significantly reduced in females smokers compared to non-smokers. Smoking alters surfactant protein and LPC/PC ratios in saliva. There is a significant difference in the effects in females compared to males. Findings suggest smoking alters the composition of saliva that may reduce protection of the oral cavity, which may explain why women smokers are at greater risk of developing oral mucositis.

Plasma surfactant protein-A levels in apparently healthy smokers, stable and exacerbation COPD patients.

Objective:To compare the plasma level of surfactant protein-A in apparently healthy smokers, stable and exacerbation Chronic Obstructive Pulmonary Disease (COPD) patients.Methods:This was a comparative study conducted from January, 2015 to March, 2016. This study was conducted on 87 subjects of both gender and age between 30-70 years. Of the total 87 subjects; 29 subjects were “healthy smokers” selected from general population as control group. Another 29 were “stable COPD” patients free of exacerbation since last six weeks. Lastly, another 29 subjects were “exacerbated COPD” patients with 7-10 days of exacerbation. COPD was diagnosed on the basis of relevant history and spirometry showing post bronchodilator FEV1/FVC <0.70. Surfactant Protein-A level (ng/ml) was estimated by a specific solid phase enzyme linked immunosorbent assay (ELISA) using automated EIA analyzer.Results:The SP-A levels, determined by competitive ELISA, was significantly higher (P<0.025) in healthy smokers (44.19±39.17 ng/ml) and exacerbated (43.86±40.17) than the stable COPD (25.89±18.85) patients. The lung function parameters (FEV1, FVC and FEV1/ FVC) were lower in COPD patients compared to healthy smokers and were related to the duration of smoking.Conclusion:Current smokers and exacerbated patients had higher values of SP-A protein than stable COPD patients since they had stopped smoking.

Obstructive Sleep Apnea and Subclinical Interstitial Lung Disease in the Multi-Ethnic Study of Atherosclerosis (MESA).

Obstructive sleep apnea (OSA) has been postulated to contribute to idiopathic pulmonary fibrosis by promoting alveolar epithelial injury via tractional forces and intermittent hypoxia. To determine whether OSA is associated with subclinical interstitial lung disease (ILD) and with biomarkers of alveolar epithelial injury and remodeling. We performed cross-sectional analyses of 1,690 community-dwelling adults who underwent 15-channel in-home polysomnography and thoracic computed tomographic imaging in the Multi-Ethnic Study of Atherosclerosis. We measured the obstructive apnea-hypopnea index (oAHI) by polysomnography and high-attenuation areas (HAAs) and interstitial lung abnormalities (ILAs) by computed tomography. Serum matrix metalloproteinase-7 (MMP-7) and surfactant protein-A (SP-A) were measured by ELISA in 99 participants. We used generalized linear models to adjust for potential confounders. The mean age was 68 years, and the mean forced vital capacity was 97% predicted. The median oAHI was 8.4 events/h, and 32% had an oAHI greater than 15. After adjusting for demographics, smoking, and center, an oAHI greater than 15 was associated with a 4.0% HAA increment (95% confidence interval [CI], 1.4-6.8%; P = 0.003) and 35% increased odds of ILA (95% CI, 13-61%; P = 0.001). However, there was evidence that these associations varied by body mass index (BMI) (P for interaction = 0.08 and 0.04, respectively). Among those with a BMI less than 25 kg/m2, an oAHI greater than 15 was associated with a 6.1% HAA increment (95% CI, 0.5-12%; P = 0.03) and 2.3-fold increased odds of ILA (95% CI, 1.3-4.1; P = 0.005). Among those with a BMI greater than 30 kg/m2, an oAHI greater than 15 was associated with 1.8-fold greater odds of ILA (95% CI, 1.1-2.9; P = 0.01) but was not associated with HAA. There were no meaningful associations detected among those with a BMI of 25-30 kg/m2. Greater oAHI was associated higher serum SP-A and MMP-7 levels, particularly among those with a BMI less than 25 kg/m2. Moderate to severe OSA is associated with subclinical ILD and with evidence of alveolar epithelial injury and extracellular matrix remodeling in community-dwelling adults, an association that is strongest among normal-weight individuals. These findings support the hypothesis that OSA might contribute to early ILD.

Effects of probiotics on ghrelin and lungs in children with acute lung injury: A double-blind randomized, controlled trial.

To assess the effects of probiotics on serum ghrelin levels and protection for lungs in children with acute lung injury (ALI). This study was performed as a double-blind, randomized, and controlled trial in a pediatric intensive care unit (PICU). The eligible children with ALI were assigned to either probiotic treatment or an identical placebo for 10 days. Serum ghrelin, SP-A(surfactant protein-A), TNF-α, and IL-6 concentrations were assessed at baseline and at the end of trial. Meanwhile, pulmonary function test and echocardiography were examined, then VPEF (volume to peak tidal expiratory flow), TPEF/TE (the ratio of time taken to reach peak expiratory flow to total expiratory time), MAP (mean arterial pressure), and PAP (pulmonary artery pressure) were recorded. Eighty participants fulfilled the study requirements with 40 children for each group. The groups were comparable in baseline characteristics. Serum SP-A, TNF-α, and IL-6 levels in the probiotic group were 212.6 ± 52.9 ng/mL, 401.9 ± 56.4 pg/mL, and 245.1 ± 55.1 pg/mL on day 10, respectively, significantly lower levels compared to the control group where the same parameters were 248.2 ± 57 ng/mL, 449.4 ± 60.1 pg/mL, and 308.3 ± 92.2 pg/mL (P < 0.01). However, ghrelin concentrations were elevated in the intervention group (P < 0.05). On measurement of pulmonary function, the probiotic group demonstrated a VPEF of 26.1 ± 4.2 mL and TPEF/TE of 29.1 ± 4.7%, which were higher than the control group (24.7 ± 4.3 mL and 26.9 ± 4.7%, respectively) (P < 0.05). MAP and PAP also improved in the probiotic group (P < 0.05). Furthermore, ghrelin, SP-A, TNF-α, IL-6, and PAP were negatively correlated. Positive correlations were found between ghrelin, TPEF/TE, and MAP. There were no probiotic-associated adverse events during the observation. Probiotics administrated to children with ALI alleviates the inflammation of lungs, improves pulmonary function and circulation by ghrelin.

Concentrations of SP-A and HSP70 are associated with polarization of macrophages in pleural effusions of non-small cell lung cancer

Damage-associated molecular pattern (DAMP) molecules can initiate an immune response through Toll-like receptors (TLRs). DAMPs are released from cells as a response to the extracellular danger and can be by-products of tissue damage. In cancer microenvironment necrotic cells release debris which has potency to become DAMPs. Non-small cell lung cancer (NSCLC) is often accompanied by pleural effusion (PE), which contains a variety of DAMPs. Surfactant protein A (SP-A) and heat shock protein 70 (Hsp70) are important DAMPs in the respiratory tract.The aim of this study was to determine a correlation between SP-A or Hsp70 and development of PE in the course of NSCLC. Moreover, we aimed to determine relationships between DAMPs and certain humoral factors associated with formation and persistence of PE as well as pleural-residing macrophages. In 34 PE samples, we estimated concentration of SP-A, Hsp70, IL-6, IL-18, G-CSF, M-CSF, SCF, SDF1α, VEGF as well as the fraction of macrophages and their pattern of polarization.We have found correlations between the concentration of the SP-A and Hsp70 and the percentage of PE-derived macrophages, also between concentrations of SP-A and Hsp70, and cytokines which participate in inflammation and processes involved in remodeling of extracellular matrix (ECM). Our data indicate an important role of SP-A during the development of PE associated with NSCLC. We suggest that measurement of concentration level of SP-A can be helpful in the course of diagnosis of malignant PE associated with NSCLC.

Obese asthmatic patients have decreased surfactant protein A levels: Mechanisms and implications

Eosinophils are prominent in some patients with asthma and are increased in the submucosa in a subgroup of obese patients with asthma (OAs). Surfactant protein A(SP-A) modulates host responses to infectious and environmental insults. We sought to determine whether SP-A levels are altered in OAs compared with a control group and to determine the implications of these alterations in SP-A levels in asthmatic patients. Bronchoalveolar lavage fluid from 23 lean, 12 overweight, and 20 obese subjects were examined for SP-A. Mouse tracheal epithelial cells grown at an air-liquid interface were used for mechanistic studies. SP-A-/- mice were challenged in allergen models, and exogenous SP-A therapy was given after the last challenge. Eosinophils were visualized and quantitated in lung parenchyma by means of immunostaining. Significantly less SP-A (P=.002) was detected in samples from OAs compared with those from control subjects. Aunivariable regression model found SP-A levels were significantly negatively correlated with body mass index (r=-0.33, P=.014), whereas multivariable modeling demonstrated that the correlation depended both on asthma status (P=.017) and the interaction of asthma and body mass index (P=.008). Addition of exogenous TNF-α to mouse tracheal epithelial cells was sufficient to attenuate SP-A and eotaxin secretion. Allergen-challenged SP-A-/- mice that received SP-A therapy had significantly less tissue eosinophilia compared with mice receiving vehicle. SP-A functions as an important mediator in resolving tissue and lavage fluid eosinophilia in allergic mousemodels. Decreased levels of SP-A in OAs, which could bedue to increased local TNF-α levels, might lead to impairedeosinophil resolution and could contribute to the eosinophilic asthma phenotype.

Lipopolysaccharide Stimulates Surfactant Protein-A in Human Renal Epithelial HK-2 Cells through Upregulating Toll-like Receptor 4 Dependent MEK1/2-ERK1/2-NF-κB Pathway.

Background:Surfactant protein-A (SP-A) contributes to the regulation of sepsis-induced acute kidney injury. In a previous study, we demonstrated that the expression of SP-A in the human renal tubular epithelial (HK-2) cells can be stimulated by lipopolysaccharide (LPS). The present study evaluated the possible signal-transducing mechanisms of LPS-induced SP-A biosynthesis in the HK-2 cells.Methods:Tetrazolium salt colorimetry (MTT) assay was used to detect cell viability of HK-2 cells after LPS stimulation on different time points. HK-2 cells were stimulated with 100 ng/ml of LPS for different durations to determine the effects of LPS on SP-A and toll-like receptor 4 (TLR4) messenger RNA (mRNA) expression, as well as phosphorylation of mitogen-activated/extracellular signal-regulated kinase (MEK) 1, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38MAPK), and nuclear factor-kappa B (NF-κB) inhibitor-alpha (IkB-α). Then, HK-2 cells were pretreated with CLI-095, a TLR4 inhibitor, to analyze mRNA and protein levels of SP-A and TLR4 and expression of NF-κB in the cytoplasm and nucleus of HK-2 before LPS exposure.Results:HK-2 cells exposed to 100 ng/ml of LPS for 1, 6, and 24 h did not affect cell viability which showed no toxic effect of 100 ng/ml LPS on cells (P = 0.16); however, the biosynthesis of SP-A mRNA and protein in HK-2 cells was significantly increased (P = 0.02). As to the mechanism, LPS enhanced transmembrane receptor TLR4 protein expression. Sequentially, LPS time dependently augmented phosphorylation of MEK1, ERK1/2, and p38MAPK. In addition, levels of phosphorylated IκB-α and nuclear NF-κB were augmented with LPS exposure for 2 h. LPS-induced SP-A and TLR4 mRNA as well as NF-κB expression were significantly inhibited by pretreatment with CLI-095.Conclusions:The present study exhibited that LPS can increase SP-A synthesis in human renal epithelial cells through sequentially activating the TLR4-related MEK1-ERK1/2-NF-κB-dependent pathway.

The effect of pressure-controlled inverse ratio ventilation on lung protection in obese patients undergoing gynecological laparoscopic surgery.

To examine the effects of pressure-controlled inverse ratio ventilation (PCIRV) and volume-control ventilation (VCV) on arterial oxygenation, pulmonary function, hemodynamics, levels of surfactant protein A (SP-A), and tumor necrosis factor-α (TNF-α) in obese patients undergoing gynecological laparoscopic surgery. Sixty patients, body mass index (BMI) ≥30kg/m2, scheduled for elective gynecological laparoscopic surgery were enrolled in the study. Patients were randomly allocated to receive either PCIRV with an inspiratory-expiratory (I:E) ratio of 1.5:1 (PCIRV group n=30) or VCV with an I:E ratio of 1:2 (VCV group n=30). Ventilation variables, viz. tidal volume (V T), dynamic respiratory-system compliance (C RS), driving pressure (ΔP=V T/C RS), arterial blood oxygen partial pressure/fraction of inspiration oxygen (PaO2/FiO2) and arterial blood carbon dioxide partial pressure (PaCO2), were measured. Hemodynamic variables, viz. mean arterial pressure (MAP), heart rate (HR), and serum levels of SP-A and TNF-α, were also measured. When compared to patients in the VCV group, patients in the PCIRV group had higher V T, dynamic CRS, and PaO2/FiO2, and lower ΔP and PaCO2 at 20 and 60min after the start of pneumoperitoneum (p<0.05). Patients in the PCIRV group had lower SP-A and TNF-α levels at 24 and 48h after surgery than those in the VCV group (p<0.05). In obese patients undergoing gynecological laparoscopic surgery, PCIRV can improve ventilation, promote gas exchange and oxygenation, and is associated with decreased levels of SP-A and TNF-α. These effects demonstrate improved lung protection provided by PCIRV in this patient population.

P239 Diagnostic potential of MMP-1 and SP-A as biomarkers to distinguish chronic hypersensitivity pneumonitis from Idiopathic pulmonary fibrosis

Introduction: Hypersensitivity pneumonitis (HP) is an inflammatory interstitial lung disease caused by a wide variety of organic particles. In general, the diagnosis of chronic HP represents a challenge for clinicians that need to use a constellation of clinical, laboratory, radiographic and pathological data to assess a confident diagnosis. Importantly, the clinical features cHP can be indistinguishable from those observed in idiopathic pulmonary fibrosis (IPF). Objective: To determine whether serum levels of surfactant protein A (SP-A) and matrix metalloprotease-1 (MMP-1) may help to differentiate cHP from IPF. Methods: This was a cross-sectional study including patients with IPF (n = 31), cHP (n = 31) and 17 healthy subjects. SP-A and MMP-1 serum levels were determined by ELISA and were evaluated for the differential diagnosis between HP and IPF, and also correlated with values of pulmonary function tests at diagnosis. Results: MMP-1 and SP-A were significantly elevated in cHP compared with the other two groups. MMP-1 (HP= 11.7 ± 14 ng/ml versus FPI= 16 ± 20.7 ng/ml, p< 0.001) and versus Controls= (0.4 ± 0.3 ng/ml, p < 0.0001), ANOVA between groups < 0.0001. SP-A (HP= 74 ± 30 pg/ml versus FPI= 54 ± 20 pg/ml, p< 0.02) and versus Controls= (35 ± 6 pg/ml, p < 0.0001), ANOVA between groups < 0.0001. There was no correlation between MMP-1 or SP-A levels with the abnormalities in pulmonary function tests. Conclusions: Our findings indicate that patients with cHP display the highest concentration of MMP-1 and SP-A which may be useful biomarkers to distinguish it from IPF.