Alveolar Epithelial Cells Type Research Articles

Pulmonary haptoglobin (pHp) is part of the surfactant system in the human lung

Since the existence of pHp was demonstrated, it has been shown that this molecule and its receptor CD163 are regulated by different stimuli. Furthermore, a comparably fast secretion of pHp was described as well as the immuno-stimulatory effects. The intention of this study was to elucidate the role of pHp in the human lungs further. Here we show, by means of confocal microscopy and immune-electron-microscopy, a clear co-localization of pHp with Surfactant protein-B in lamellar bodies of Alveolar Epithelial Cells Type II. These results are underlined by immunohistochemical stainings in differently fixed human lung tissues, which show pHp in vesicular and released form. The images of the released form resemble the intended position of surfactant in the human alveolus. pHp is secreted by Alveolar epithelial cells type II as previously shown. Moreover, pHp is co-localized with Surfactant protein-B. We conclude that the presented data shows that pHp is a native part of the surfactant system in the human lung.Virtual slideshttp://www.diagnosticpathology.diagnomx.eu/vs/2563584738239912.

Hermansky-Pudlak Syndrome Interstitial Pneumonia

Hermansky-Pudlak Syndrome Interstitial Pneumonia

Influence of Phosphodiesterase-Inhibitor PDE4 Roflumilast N-Oxide on Surfactant Protein of human Alveolar Epithelial Cell Type II

Surfactant Proteins (SPs) are surface active lipoproteins, essential for the integrity of the lung and important for host defence. All four Surfactant Proteins (A-D) and their isoforms are mainly expressed by alveolar epithelial cells type II (AECII). It has been shown that SP gene transcription is regulated by intracellular cyclic adenosine monophosphate (cAMP).

Roflumilast-N-oxide Induces Surfactant Protein Expression in Human Alveolar Epithelial Cells Type II

Surfactant proteins (SPs) are important lipoprotein complex components, expressed in alveolar epithelial cells type II (AEC-II), and playing an essential role in maintenance of alveolar integrity and host defence. Because expressions of SPs are regulated by cyclic adenosine monophosphate (cAMP), we hypothesized that phosphodiesterase (PDE) inhibitors, influence SP expression and release. Analysis of PDE activity of our AEC-II preparations revealed that PDE4 is the major cAMP hydrolysing PDE in human adult AEC-II. Thus, freshly isolated human AEC-II were stimulated with two different concentrations of the PDE4 inhibitor roflumilast-N-oxide (3 nM and 1 µM) to investigate the effect on SP expression. SP mRNA levels disclosed a large inter-individual variation. Therefore, the experiments were grouped by the basal SP expression in low and high expressing donors. AEC-II stimulated with Roflumilast-N-oxide showed a minor increase in SP-A1, SP-C and SP-D mRNA mainly in low expressing preparations. To overcome the effects of different basal levels of intracellular cAMP, cyclooxygenase was blocked by indomethacin and cAMP production was reconstituted by prostaglandin E2 (PGE2). Under these conditions SP-A1, SP-A2, SP-B and SP-D are increased by roflumilast-N-oxide in low expressing preparations. Roflumilast-N-oxide fosters the expression of SPs in human AEC-II via increase of intracellular cAMP levels potentially contributing to improved alveolar host defence and enhanced resolution of inflammation.

Role of autophagy in the development of amiodarone induced pulmonary fibrosis

Introduction: Amiodarone (AD) is a well known anti arrhythmic drug, but is limited by its potential side effects. Severe pulmonary toxicity is reported in patients receiving amiodarone, with the most common histological finding being chronic interstitial pneumonia. Apoptosis of alveolar epithelial cells type II (AECII) was reported in a rat model of amiodarone induced pulmonary toxicity. However, the underlying molecular mechanisms remain unknown. We aimed to establish a mouse model for AD induced pulmonary fibrosis and study the involved molecular mechanisms.

Age-Dependent Decline in Mouse Lung Regeneration with Loss of Lung Fibroblast Clonogenicity and Increased Myofibroblastic Differentiation

While aging leads to a reduction in the capacity for regeneration after pneumonectomy (PNX) in most mammals, this biological phenomenon has not been characterized over the lifetime of mice. We measured the age-specific (3, 9, 24 month) effects of PNX on physiology, morphometry, cell proliferation and apoptosis, global gene expression, and lung fibroblast phenotype and clonogenicity in female C57BL6 mice. The data show that only 3 month old mice were fully capable of restoring lung volumes by day 7 and total alveolar surface area by 21 days. By 9 months, the rate of regeneration was slower (with incomplete regeneration by 21 days), and by 24 months there was no regrowth 21 days post-PNX. The early decline in regeneration rate was not associated with changes in alveolar epithelial cell type II (AECII) proliferation or apoptosis rate. However, significant apoptosis and lack of cell proliferation was evident after PNX in both total cells and AECII cells in 24 mo mice. Analysis of gene expression at several time points (1, 3 and 7 days) post-PNX in 9 versus 3 month mice was consistent with a myofibroblast signature (increased Tnc, Lox1, Col3A1, Eln and Tnfrsf12a) and more alpha smooth muscle actin (αSMA) positive myofibroblasts were present after PNX in 9 month than 3 month mice. Isolated lung fibroblasts showed a significant age-dependent loss of clonogenicity. Moreover, lung fibroblasts isolated from 9 and 17 month mice exhibited higher αSMA, Col3A1, Fn1 and S100A expression, and lower expression of the survival gene Mdk consistent with terminal differentiation. These data show that concomitant loss of clonogenicity and progressive myofibroblastic differentiation contributes to the age-dependent decline in the rate of lung regeneration.

Pulmonary Haptoglobin and CD163 Are Functional Immunoregulatory Elements in the Human Lung

Background: The acute-phase protein haptoglobin (Hp) and its receptor CD163 serve as immunomodulators and possess anti-inflammatory besides antioxidant functions. Objectives: To further understand the role of the recently described pulmonary Hp (pHp) and its receptor CD163 in case of inflammation and infection, pHp and CD163 were investigated on mRNA and protein level to gain insight into the cellular events taking place upon stimulation with the inflammatory mediators LPS, Pam3, cytokine IL-6 and dexamethasone, and upon infection with respiratory pathogens (Haemophilus influenzae, Streptococcuspneumoniae and Chlamydia pneumoniae) by use of a human ex vivo tissue culture model and cell cultures of A549 and alveolar epithelial cells type II. In addition, pHp and CD163 expression in COPD and sarcoidosis was assessed. Methods: We conducted experiments using 942 ex vivo cultured lung samples applying immunohistochemistry, immunocytochemistry, in situ hybridization, immunofluorescence, real-time PCR, RT-PCR, slot and Western immunoblot analyses with tissue lysates and culture supernatants as well as ELISA and cytometric bead array analyses. Results: This study describes for the first time the expression, regulation and secretion of pHp and its receptor CD163 in the human lung. The release of soluble mediators from A549 cell line and human monocyte-derived macrophages was observed indicating that Hp differentially activates the release of soluble mediators and major chemoattractants. Conclusions: The findings indicate a native function of pHp and CD163 as functional pulmonary defense elements due to local expression, regulation and secretion during lung infection and as part of the inflammatory immune response of the respiratory system.

Generation and evaluation of a monoclonal antibody, designated MAdL, as a new specific marker for adenocarcinomas of the lung

Background:Different therapy regimens in non-small-cell lung cancer (NSCLC) are of rising clinical importance, and therefore a clear-cut subdifferentiation is mandatory. The common immunohistochemical markers available today are well applicable for subdifferentiation, but a fraction of indistinct cases still remains, demanding upgrades of the panel by new markers.Methods:We report here the generation and evaluation of a new monoclonal antibody carrying the MAdL designation, which was raised against primary isolated human alveolar epithelial cells type 2.Results:Upon screening, one clone (MAdL) was identified as a marker for alveolar epithelial cell type II, alveolar macrophages and adenocarcinomas of the lung. In a large-scale study, this antibody, with an optimised staining procedure for formalin-fixed tissues, was then evaluated together with the established markers thyroid transcription factor-1, surfactant protein-A, pro-surfactant protein-B and napsin A in a series of 362 lung cancer specimens. The MAdL displays a high specificity (>99%) for adenocarcinomas of the lung, together with a sensitivity of 76.5%, and is capable of delivering independent additional diagnostic information to the established markers.Conclusion:We conclude that MAdL is a new specific marker for adenocarcinomas of the lung, which helps to clarify subdifferentiation in a considerable portion of NSCLCs.

The Milieu of Damaged Alveolar Epithelial Type 2 Cells Stimulates Alveolar Wound Repair by Endogenous and Exogenous Progenitors

Alveolar epithelial integrity is dependent upon the alveolar milieu, yet the milieu of the damaged alveolar epithelial cell type 2 (AEC2) has been little studied. Characterization of its components may offer the potential for ex vivo manipulation of stem cells to optimize their therapeutic potential. We examined the cytokine profile of AEC2 damage milieu, hypothesizing that it would promote endogenous epithelial repair while recruiting cells from other locations and instructing their engraftment and differentiation. Bronchoalveolar lavage and lung extract from hyperoxic rats represented AEC2 in vivo damage milieu, and medium from a scratch-damaged AEC2 monolayer represented in vitro damage. CINC-2 and ICAM, the major cytokines detected by proteomic cytokine array in AEC2 damage milieu, were chemoattractive to normoxic AECs and expedited in vitro wound healing, which was blocked by their respective neutralizing antibodies. The AEC2 damage milieu was also chemotactic for exogenous uncommitted human amniotic fluid stem cells (hAFSCs), increasing migration greater than 20-fold. hAFSCs attached within an in vitro AEC2 wound and expedited wound repair by contributing cytokines migration inhibitory factor and plasminogen activator inhibitor 1 to the AEC2 damage milieu, which promoted wound healing. The AEC2 damage milieu also promoted differentiation of a subpopulation of hAFSCs to express SPC, TTF-1, and ABCA3, phenotypic markers of distal alveolar epithelium. Thus, the microenvironment created by AEC2 damage not only promotes autocrine repair but also can attract uncommitted stem cells, which further augment healing through cytokine secretion and differentiation.

Salt-inducible kinase 1 is present in lung alveolar epithelial cells and regulates active sodium transport

Salt-inducible kinase 1 (SIK1) in epithelial cells mediates the increases in active sodium transport (Na+, K+-ATPase-mediated) in response to elevations in the intracellular concentration of sodium. In lung alveolar epithelial cells increases in active sodium transport in response to β-adrenergic stimulation increases pulmonary edema clearance. Therefore, we sought to determine whether SIK1 is present in lung epithelial cells and to examine whether isoproterenol-dependent stimulation of Na+, K+-ATPase is mediated via SIK1 activity. All three SIK isoforms were present in airway epithelial cells, and in alveolar epithelial cells type 1 and type 2 from rat and mouse lungs, as well as from human and mouse cell lines representative of lung alveolar epithelium. In mouse lung epithelial cells, SIK1 associated with the Na+, K+-ATPase α-subunit, and isoproterenol increased SIK1 activity. Isoproterenol increased Na+, K+-ATPase activity and the incorporation of Na+, K+-ATPase molecules at the plasma membrane. Furthermore, those effects were abolished in cells depleted of SIK1 using shRNA, or in cells overexpressing a SIK1 kinase-deficient mutant. These results provide evidence that SIK1 is present in lung epithelial cells and that its function is relevant for the action of isoproterenol during regulation of active sodium transport. As such, SIK1 may constitute an important target for drug discovery aimed at improving the clearance of pulmonary edema.

A 10-Gene Progenitor Cell Signature Predicts Poor Prognosis in Lung Adenocarcinoma

One aspect of the cancer stem cell hypothesis is that patients with tumors that exhibit stem-like phenotypes have poor prognoses. Distal epithelial progenitors from lungs early in development demonstrate both self-renewal and potential to differentiate into all bronchial and alveolar epithelial cell types. By contrast, late progenitors are only able to produce alveolar cells. We sought to create a lung-specific progenitor cell signature for possible prognosis prediction in human lung cancer. A transgenic mouse was created in which embryonic distal epithelial progenitor cells express green fluorescent protein when tamoxifen is administered. Lung progenitor cells were harvested after tamoxifen injection at either embryonic day 11.5 (E11.5) or 17.5 (E17.5). The RNA extracted from these cells was hybridized to Affymetrix 430.2 mouse chips (Affymetrix, Santa Clara, CA). A genomic signature was created by comparing the cell types using L1 logistic regression and applied to transcriptome datasets of resected patients from our tumor bank and the National Institutes of Health Director's Challenge Consortium. When a 10-gene genomic signature was applied to resected human adenocarcinoma datasets, tumors that were transcriptionally similar to the early progenitors had a significantly worse prognosis than those similar to the late progenitors. Using a Cox model in which age and stage were included, the predicted score from the logistic regression model was an independent predictor of survival. A lung progenitor cell signature predicts poor prognosis in lung adenocarcinoma. Modulation of these genes or their signaling pathways may be effective therapeutic strategies in the future.

All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages

All-trans retinoic acid (ATRA) is controversially discussed in emphysema therapy. We re-evaluated ATRA in the elastase model and hypothesised that beneficial effects should be reflected by increased alveolar surface area, elastin expression and downregulation of inflammatory mediators and matrix metalloproteinases (MMPs). Emphysema was induced by porcine pancreatic elastase versus saline in Sprague-Dawley rats. On days 26-37, rats received daily intraperitoneal injections with ATRA (500 μg · kg(-1) body weight) versus olive oil. Lungs were removed at day 38. Rat alveolar epithelial L2 cells were incubated with/without elastase followed by ATRA- or vehicle-treatment, respectively. ATRA only partially ameliorated structural defects. Alveolar walls exhibited irregular architecture: increased arithmetic mean thickness, reduction in surface coverage by alveolar epithelial cells type II. ATRA only partially restored reduced soluble elastin. It tended to increase the ratio of ED1(+):ED2(+) macrophages. Bronchoalveolar lavage (BAL) cells exhibited a proinflammatory state and high expression of interleukin-1β, cytokine-induced neutrophil chemoattractant-1, tumour necrosis factor-α, nuclear factor-κB, MMP-2, MMP-9, MMP-12, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in emphysema, with ATRA exerting only few effects. MMP-7 was highly induced by ATRA in healthy but not in emphysematous lungs. ATRA reduced both MMP-2 and TIMP-1 activity in BAL fluid of emphysematous lungs. ATRA-therapy may bear the risk of unwanted side-effects on alveolar septal architecture in emphysematous lungs.

Increased expression of epidermal fatty acid-binding protein by alveolar macrophages during acute rejection of rat lungs

In the lung, epidermal fatty acid-binding protein (E-FABP) is expressed by alveolar macrophages (AM) and alveolar epithelial cells type II (AEII). E-FABP may regulate macrophage activation and is involved in the metabolism of surfactant phospholipids. As macrophage activation and surfactant dysfunction are associated with rejection, we hypothesize that E-FABP expression is changed during acute rejection of pulmonary grafts. Orthotopic left lung transplantations were performed in the Dark Agouti to Lewis and in the isogeneic Lewis to Lewis rat strain combinations. E-FABP expression was analyzed in the lung by immunohistochemistry, immunoblotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR). Alveolar leukocytes obtained by bronchoalveolar lavage were analyzed by RT-PCR. Immunohistochemistry of isografts revealed strong E-FABP immunoreactivity in AEII and a moderate immunoreactivity in AM. In allografts undergoing acute rejection, AM exhibiting increased E-FABP immunoreactivity accumulated. Immunoblots revealed a single band at 15 kDa, which corresponds to the expected molecular mass of E-FABP. The levels of E-FABP mRNA were higher in allografts than in isografts and control lungs. Furthermore, alveolar leukocytes isolated by bronchoalveolar lavage from allografts displayed higher E-FABP mRNA expression levels than leukocytes from isografts and controls. In conclusion, we demonstrate for the first time upregulation of E-FABP expression in AM during severe inflammation.

Surfactant lipids regulate LPS-induced interleukin-8 production in A549 lung epithelial cells by inhibiting translocation of TLR4 into lipid raft domains

In addition to providing mechanical stability, growing evidence suggests that surfactant lipid components can modulate inflammatory responses in the lung. However, little is known of the molecular mechanisms involved in the immunomodulatory action of surfactant lipids. This study investigates the effect of the lipid-rich surfactant preparations Survanta, Curosurf, and the major surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) on interleukin-8 (IL-8) gene and protein expression in human A549 lung epithelial cells using immunoassay and PCR techniques. To examine potential mechanisms of the surfactant lipid effects, Toll-like receptor 4 (TLR4) expression was analyzed by flow cytometry, and membrane lipid raft domains were separated by density gradient ultracentrifugation and analyzed by immunoblotting with anti-TLR4 antibody. The lipid-rich surfactant preparations Survanta, Curosurf, and DPPC, at physiological concentrations, significantly downregulated lipopolysaccharide (LPS)-induced IL-8 expression in A549 cells both at the mRNA and protein levels. The surfactant preparations did not affect the cell surface expression of TLR4 or the binding of LPS to the cells. However, LPS treatment induced translocation of TLR4 into membrane lipid raft microdomains, and this translocation was inhibited by incubation of the cells with the surfactant lipid. This study provides important mechanistic details of the immune-modulating action of pulmonary surfactant lipids.

On the expression of haptoglobin in the human lungs

Introduction: The acute phase protein Haptoglobin (Hp) consists of two different polypeptide chains. Originating from the liver; the biological function is binding free hemoglobin (Hb) and preventing oxidative stress. Elevated amounts of Hp in plasma were observed were infection, inflammation and malignant diseases. Purpose of this study was to investigate protein and mRNA expression within human lung tissues and tumors. Methods: We performed immunohistochemistry, in situ hybridization and RT-PCR analyzing 115 tissue samples. 47 adenocarcinomas, 42 squamous cell carcinomas, 13 small cell lung cancers and 13 tumor-free lungs were investigated. After lobectomy/pneumonectomy tissues were fixed and paraffin-embedded using formalin (immunohistochemistry) or the HOPE-solution (other methods). Results: Immunohistochemistry and in situ hybridization revealed a high level of Hp expression in adenocarcinomas (40.4%) in contrast to squamous cell carcinomas (4.8%, expression in alveolar epithelial cells type II surrounding the tumor). One small cell carcinoma showed Hp expression. In tumor-free lungs we located Hp in alveolar macrophages; alveolar epithelial cells type II and bronchi. RT-PCR results confirmed elevated expression. Discussion: We characterized that Hp protein expressed in lung cancers and tumor-free lungs showing an extra hepatic function. Due to the known immunosuppressive properties of Hp, its broad synthesis is strongly suggestive for a function as a fundamental, pulmonary, local defense element and confirms recent reports that haptoglobin plays an important role in protection processes and repairing mechanisms of injured tissues.

The Alveolar Epithelium and Pulmonary Fibrosis

Idiopathic interstitial pneumonias (IIPs) are a heterogeneous group of diffuse pulmonary parenchymal diseases that are comprised of seven distinct clinical and pathological entities. Idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP) represent two of the most prevalent members of the disease group with major differences in their pathogenesis, clinical course and prognosis. IPF is a refractory and lethal IIP characterized by fibroblast prolifera- tion, deposition of extracellular matrix (ECM) and progressive lung scarring. The incidence of IPF is estimated at 15 to 40 cases per 100,000 per year, and the mean survival from the time of diagnosis is 3 to 5 years regardless of treatment. While its pathogenesis is incompletely understood, the currently accepted paradigm proposes that injury of the alveolar epithe- lium is followed by a burst of pro-inflammatory and fibroproliferative mediators that invoke responses associated with dysregulated repair of the damaged alveolar epithelium. Recently, there have been studies suggesting that the activation of the alveolar epithelial cells (AECs) may play an active role in the pathogenesis of pulmonary fibrosis. Here, we review the advances in recent studies on the role of the alveolar epithelium in pulmonary fibrosis. AECS: A BRIEF OVERVIEW OF STRUCTURE AND PHYSIOLOGICAL FUNCTIONS Two types of AECs populate the alveolar epithelium in normal adult lungs, alveolar epithelial type I (AT I) and al- veolar epithelial type II (AT II) cells. AT I pneumocytes comprise 40% of the AECs and cover 90% of the internal surface area of the lung. AT I cells are highly attenuated and form an interface with pulmonary capillaries that are inti- mately involved in gas exchange. These cells also take part in peptide and amino acid transportation across the lung by pinocytosis and transporter-mediated transport (1). Recently, AT I cells have been shown to be also important in the trans- portation of water and sodium across the lung (2, 3). AT II cells, on the other hand, AT II cells make up 16% of the parenchymal cells in the lung and account for only 5% of the alveolar surface. These cells are cuboidal cells that are situated between AT I cells and they contain characteristic lamellar bodies and apical microvilli. AT II cells synthesize, store and secrete the pulmonary surfactant (PS), which con- sists of lipids and their associated proteins and whose func- tion is to reduce the surface tension of the lung alveolus and prevent it from collapse or overdistension with respiration. AT II cells also regulate alveolar fluid balance in normal lungs and during the resolution of pulmonary edema (4) and the pathogenesis of acute lung injury with pulmonary edema is associated with an insufficient number of AT II cells and transportation of water into the lung alveolus. Recently, AT II cells have been shown to synthesize and secrete immuno- modulatory proteins important for host defense, including surfactant proteins A (SP-A) and D (SP-D) (5). SP-A can combine with lipid A in the lipopolysaccharide on the sur- face of bacterium and it also regulates the activities of

Expression of the acute phase protein haptoglobin in human lung cancer and tumor-free lung tissues

Besides its main function, i.e., the binding of free hemoglobin and prevention of oxidative stress, the acute phase protein haptoglobin acts as a potent immunoreactive modulator. As part of an investigation that aimed at illuminating the role of acute phase proteins in the local defense of the lungs, this study is the first to describe the expression and synthesis of haptoglobin in human lung tissues and lung tumors. Prompted by the results obtained from a transcription array study, we analyzed 115 lung (cancer) specimens using immunohistochemistry. Thirty-seven specimens were subjected to mRNA- in situ hybridization. 40.4% of the adenocarcinomas showed distinct granular and perinuclear staining of the tumor cells. By contrast, only 4.8% of the squamous cell carcinomas showed haptoglobin within tumor cells, but 19% displayed haptoglobin expressing alveolar epithelial cells type II surrounding the tumor. One small cell lung cancer displayed haptoglobin expression. In tumor-free lungs, we located haptoglobin in alveolar macrophages, alveolar epithelial cells type II, and bronchiolar cells. In situ hybridization verified the results of immunohistochemistry. The results were further verified by RT-PCR and Western blot compared to liver tissues, which both showed comparable amounts of haptoglobin mRNA and protein in NSCLC and in liver, while tumor-free lung tissues showed lower expression. Due to the known immunomodulatory effects of haptoglobin, its broad expression and synthesis within human lung tissues strongly suggests a function as a fundamental pulmonary local defense element.

Static Stretch Induces Active Morphological Remodeling and Functional Impairment of Alveolar Epithelial Cells

Background: Static stretch is frequently observed in the lung. Both static stretch and cyclic stretch can induce cell death and Na⁺/K⁺-ATPase trafficking, but stretch-induced alveolar epithelial cell (AEC) functions are much less responsive to static than to cyclic stretch. AEC remodeling under static stretch may be partly explained. Objective: The aim of this study was to explore the AEC remodeling and functional changes under static stretch conditions. Method: We used A549 cells as a model of AEC type II cells. We assessed F-actin content and cell viability by fluorescence staining at various static-stretch magnitudes and time points. Specifically, we used scanning electron microscopy to explore the possible biological mechanisms used by A549 cells to ‘escape’ static-stretch-induced injury. Finally, we measured choline cytidylyltransferase-α (CCTα) mRNA and protein by real-time PCR and Western blot to evaluate cellular secretory function. Results: The results showed that the magnitude of static stretch was the primary determinant of static-stretch-induced cell death and cytoskeleton organization, but an extended duration of high static deformation/stretch (37% change in surface area) had no cumulative effects on cell death and cytoskeleton organization. AEC remodeling (expansion-contraction-reexpansion) under static stretch conditions may explain this interesting phenomenon partly. After cell remodeling, CCTα expression in A549 cells was influenced not only by stretch magnitude but also by stretch time. Conclusion: Under static stretch conditions, A549 cells undergo morphological and functional changes. They can survive stress failure from overstretching by remodeling their body to ‘escape’ the injury. During this complex course of remodeling, cellular function was partly damaged.

On the significance of Surfactant Protein-A within the human lungs

Surfactant Protein-A (SP-A) is the most prominent among four proteins in the pulmonary surfactant-system. SP-A is expressed by alveolar epithelial cells type II as well as by a portion of non small cell lung carcinomas (NSCLC).The expression of SP-A is complexly regulated on the transcriptional and the chromosomal level. SP-A is a major player in the pulmonary cytokine-network and moreover has been described to act in the pulmonary host defense.By the use of cell culture or animal models the functional properties have been repeatedly shown in many aspects, often bearing surprising properties which strongly indicate the physiological importance of SP-A. To date SP-A is recognized as a molecule essential for pulmonary development, structure and function. An upcoming number of reports deals with the role of SP-A for pulmonary pathology. This article gives an overview about the state of knowledge on SP-A focused in applications for human pulmonary disorders and points out the importance for pathology-orientated research approaches using immunohistochemistry or in situ hybridization as promising methods to further elucidate the role of this molecule in adult lung diseases.

The advancement in reparing of alveolar epithelial cell type II injury induced by hyperoxia

高氧导致的肺泡Ⅱ型上皮细胞(AECⅡ)损伤主要与活性氧生成增多引起膜脂质过氧化、促炎症因子释放、抑制细胞增殖与分化有关,从而引起支气管肺发育不良、肺纤维化等慢性肺疾病.肺上皮的修复过程依赖AECⅡ的铺展、迁移和增殖,使肺泡再卜皮化.与AECⅡ修复有关的生理因素包括生长因子类(如角化细胞生长因子和肝细胞生长因子)、基质金属蛋白酶类、体内纤溶活性、气道神经肽及端粒酶等.此外,维持上皮.成纤维细胞功能平衡在高氧肺损伤修复中亦具有重要意义.AECⅡ还能转分化为AEC I,以补充损伤的肺泡上皮.骨髓或循环血中干细胞在肿损伤后能获得AEC的表型特征,在介导肺上皮修复的过程中可能亦具有重要意义。