Surfactant-associated Protein Research Articles

Lucinactant for the treatment of respiratory distress syndrome in neonates

Respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in premature neonates. This syndrome is caused by a lack of endogenous surfactant production in the lungs. Surfactant replacement was established as a safe and effective treatment in the 1990s and has become the standard of care for these infants. Surfactant products are either protein-free synthetic phospholipid compounds or animal-derived lung preparations. Currently, about 90,000 infants a year receive treatment with one of the commercially available animal-derived surfactants. Lucinactant (Surfaxin®) is a new synthetic surfactant with a pulmonary surfactant-associated protein B mimic that recently received FDA approval. The clinical trials that have been performed, although underpowered, may indicate that lucinactant is superior to phospholipid synthetic surfactant preparations and at least as effective as animal-derived surfactants in reducing morbidity and mortality from RDS. This review summarizes the current clinical knowledge about lucinactant.

Roles of vascular endothelial growth factor and dexamethasone in expressions of surfactant protein B and transforming growth factor-β1 in type II alveolar epithelial cells

Objective To investigate the effects of vascular endothelial growth factor (VEGF) and dexamethasone on mRNA expressions of surfactant protein B (SP-B) and transforming growth factor-β1 (TGF-β1) of type Ⅱ alveolar epithelial cell (AECⅡ). Methods AECⅡ were isolated and purified from fetal rat lung tissues,then cultured with different dose of VEGF (25,50 and 100 ng/ml) and dexamethasone (25,50,100 and 200 nmol/ml).The mRNA levels of SP-B and TGF-β1 were detected by real-time quantitative polymerase chain reaction (RT-PCR) and expression of TGF-β1 protein was detected by immunocytochemistry.ANOVA or q-test was applied to compare the difference among groups.Results Compared with control group,SP-B mRNA levels in 25 ng/ml VEGF group and 25,50,100 and 200 nmol/ml dexamethasone groups were higher (13.500±3.172,3.547±0.690,5.219±0.782,3.493±0.335,and 3.981 ± 1.133 vs 1.001 ± 0.059,q=-5.286,-4.943,- 7.228,- 9.906 and - 3.525 respectively,P＜0.05) ; TGF-β1 mRNA expression of 25 ng/ml VEGF group,50,100 and 200 nmol/ml dexamethasone group was lower (0.451 ± 0.078,0.579±0.019,0.422 ± 0.020 and 0.769 ± 0.025 vs 1.019±0.226,q=4.110,3.356,4.551 and 1.901 respectively,P＜0.05) ; other groups had no significant differences compared with control group (P＞0.05).Immunocytochemistry showed that the positive rate of TGF-β1 expression in 25 ng/ml VEGF,50,100 and 200 nmol/ml dexamethasone group was 23％,26％,22％ and 29％,respectively,while in the control group,the expression of TGF-β1 was positive in most of the AECⅡ (80％).Conclusions Both VEGF and dexamethasone could increase the expression of SP-B at mRNA level at appropriate concentrations.At the same time,the expression of TGF-β1 is inhibited.It is suggested that both VEGF and dexamethasone might increase the mRNA expression of SP-B by inhibiting the expression of TGF-β1. Key words: Pulmonary alveoli; Pulmonary surfactant-associated protein B; Transforming growth factor beta 1 ; Vascular endothelial growth factor A; Daxamethasone

Respiratory effects associated with wood fuel use: A cross‐sectional biomarker study among adolescents

The use of wood as heating and cooking fuel can result in elevated levels of indoor air pollution, but to what extent this is related to respiratory diseases and allergies is still inconclusive. Here, we report a cross-sectional study among 744 school adolescents (median age 15 years) using as main outcomes respiratory symptoms and diseases, exhaled nitric oxide, total and aeroallergen-specific IgE in serum, and two epithelial biomarkers in nasal lavage fluid (NALF) or serum, that is, Clara cell protein (CC16) and surfactant-associated protein D (SPD). Information about the wood fuel use and potential confounders was collected via a personal interview of the adolescent and a questionnaire filled out by the parents. Two approaches were used to limit the possible influence of confounders, that is, multivariate analysis using the complete study population or pairwise analysis of matched sub-populations obtained using an automated procedure. Wood fuel use was associated with a decrease of CC16 and an increase of SPD in serum, which resulted in a decreased serum CC16/SPD ratio (median -9%, P = 0.001). No consistent differences were observed for the biomarkers measured in exhaled breath or NALF. Wood fuel use was also associated with increased odds for asthma [odds ratio (OR) 2.2, 95% CI: 1.1-4.4, P = 0.02], hay fever (OR = 2.4, 95% CI: 1.4-4.3, P = 0.002), and sensitization against pollen allergens (OR = 2.1, 95% CI: 1.3-3.4, P = 0.002). The risks of respiratory tract infections, self-reported symptoms, and sensitization against house-dust mite were not increased by wood fuel use. The increased risks of asthma, hay fever and aeroallergen sensitization, and the changes of lung-specific biomarkers consistently pointed towards respiratory effects associated with the use of wood fuel.

Histopathological and immunohistochemical study of cattle tuberculosis and expression of surfactant-associated proteins (SP)

Histopathological and immunohistochemical study of cattle tuberculosis and expression of surfactant-associated proteins (SP)

Indispensable role of factor for adipocyte differentiation 104 (fad104) in lung maturation

Factor for adipocyte differentiation 104 (fad104) is a regulator of adipogenesis and osteogenesis. Our previous study showed that fad104-deficient mice died immediately after birth, suggesting fad104 to be essential for neonatal survival. However, the cause of this rapid death is unclear. Here, we demonstrate the role of fad104 in neonatal survival. Phenotypic and morphological analyses showed that fad104-deficient mice died due to cyanosis-associated lung dysplasia including atelectasis. Furthermore, immunohistochemistry revealed that FAD104 was strongly expressed in ATII cells in the developing lung. Most importantly, the ATII cells in lungs were immature, and impaired the expression of surfactant-associated proteins. Collectively, these results indicate that fad104 has an indispensable role in lung maturation, especially the maturation and differentiation of ATII cells.

The milky (path)way of proteinosis: has the time come

After having read the paper by Borie et al. [1] in this issue of European Respiratory Review , I decided not to write a classic scientific editorial. It is often difficult to write an editorial comment for a review article, and in this case even more so since the paper by Borie et al. [1] is one of the most comprehensive and up-to-date reviews on pulmonary alveolar proteinosis (PAP) since the milestone article of Seymour and Presneill [2]. What could I add or how would I comment on the achievement that lung biopsy is now no longer required to diagnose typical forms of autoimmune PAP? Or that the passive transfer of human granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (GMAbs) to monkeys reproduces features typical of PAP, thus, supporting the pathogenic role of GMAbs [3]? Or that several surfactant-associated genes and proteins may be involved not only in proteinosis, but also in other forms of interstitial lung diseases [4]? Beyond the intrinsic value of the scientific information, the review by Borie et al. [1] also has the …

Serum pneumoproteins in firefighters

Serum Clara cell protein (CC16) and surfactant-associated protein A (SP-A) were measured in a cross-sectional study in 402 firefighters. For the population as a whole, no associations were detected between serum pneumoproteins and smoke exposure. SP-A levels were increased in symptomatic subjects exposed to fire smoke within 2 days before testing. SP-A levels were higher after an inhalation incident ever. CC16 was negatively associated with the number of fires fought in the last 12 months in current nonsmokers. These associations between pneumoprotein levels reiterate the importance of adequate use of self-contained breathing apparatus by firefighters.

Expression of pulmonary surfactant protein A mRNA in lungs of fetal rats with maternal intrahepatic cholestasis

Objective To investigate the pulmonary morphologic changes and pulmonary surfactant protein A (SP-A) mRNA expression in fetal rats with maternal intrahepatic cholestasis of pregnancy (ICP).Methods Animal models of intrahepatic cholestasis of pregnancy were induced by 17-α-ethinylestradiol and progesterone.Histopathologic examination of the fetal lungs was performed under light and electronic microscopes.The expression of SP-A mRNA in the fetal lungs was measured by reverse transcription-polymerase chain reaction technique.Results (1) Compared with the control group,histopathologic examination showed that fetal pulmonary tissues had dilated and congested interstitial lung capillaries,thickened alveolar septum,mild focal inflammatory exudation and focal hemorrhage in alveolus.Furthermore,reduced microvilli,mitochondrion vacuolization,cytoplasm disintegration and increased lamellar body evacuation were observed in alveolar epithelial cell II in ICP group under light and electronic microscopes.(2) Expression of SP-A mRNA in fetal lungs of ICP group (0.71 + 0.10) was significantly lower than that in control group (1.00±0.27),t=3.093,P＜0.05.Conclusions Hyperbileacidemia in ICP maternal rat might lead to pathological changes in fetal pulmonary tissues.Low expression of SP-A mRNA might contribute to lesions of fetal lung with ICP. Key words: Pregnancy complications; Cholestasis,intrahepatic; Pulmonary surfactantassociated protein A; RNA,messenger; Rats

Novel gene fad104 is required for lung morphogenesis

Previously, we identified fad104 (factor for adipocyte differentiation 104) as a novel gene whose expression was induced in the early stage of adipogenesis. Mouse fad104 encodes a 132‐kDa protein, which contains nine fibronectin type III domains and a transmembrane region. We have reported that fad104 promotes adipogenesis and that deletion of fad104 causes neonatal death. However, the cause of death in fad104‐deficient mice is unclear. Here, we attempted to clarify the cause of death in fad104‐deficient mice, and uncover the physiological role of fad104.□@ First, phenotypic and morphological analyses showed that fad104‐deficient pups displayed cyanosis and died from respiratory distress immediately after birth. In addition, fad104‐deficient lungs were small and its alveolar spaces were not dilated adequately. Furthermore, we revealed that FAD104 was expressed in alveolar epithelial type II (ATII) cells in the developing lungs. Moreover, the ATII cells in fad104‐deficient lungs were immature and attenuated the expression of surfactant‐associated proteins.In conclusion, this work demonstrated that fad104 has a crucial role in lung morphogenesis at least in part by regulating ATII cell maturation.

Troglitazone-activated PPARγ inhibits LPS-induced lung alveolar type II epithelial cells injuries via TNF-α

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are common syndromes characterized by diffuse, acute injury to the alveolar epithelium and pulmonary vascular endothelial cells, with high mortality rate for there are no effective pharmacological therapies. Peroxisome proliferators-activated receptor γ (PPARγ), a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors, is ubiquitously expressed within the lung. Recent studies have indicated PPARγ can protect lung tissue and alleviate pulmonary inflammatory injury. But no studies examined whether PPARγ agonists can protect the alveolar epithelial cells cultured in vitro. We observed the protective effect of PPARγ in LPS-induced alveolar type II epithelial cells injury. The results showed troglitazone-activated PPARγ could inhibit the production of TNF-α, one of the most important inflammatory factors, and then increased the expression of surfactant-associated protein A (SP-A) and attenuate the apoptosis of alveolar type II epithelial cells. Our results suggest that PPARγ may have a potential therapeutic effect on ALI.

JUN-CCAAT/Enhancer-Binding Protein Complexes Inhibit Surfactant-Associated Protein B Promoter Activity

The murine surfactant-associated protein B (Sftpb) gene promoter, spanning nucleotides -653 to +42, is composed of functionally distinct proximal and distal regions. Although both regions contain consensus/putative activator protein 1 (AP-1) sites, the distal, but not the proximal, region mediates the inhibition by jun proto-oncogene (JUN) of Sftpb promoter activity. In transient cotransfection assays, JUN inhibited the luciferase reporter activity of plasmid constructs containing Sftpb promoter fragments that lacked the distal putative AP-1 site, indicating that another regulatory motif mediates JUN-dependent inhibition. Electrophoretic mobility shift assays and in silico analyses identified a DNA target sequence (Sftpb nucleotides -339 to -316) and transcription factors that regulate Sftpb promoter activity. The identified sequence contains a CCAAT/enhancer-binding protein (C/EBP) consensus recognition element. Mutation of the site reduced Sftpb promoter activity and sensitivity to inhibition by JUN. Purified recombinant JUN, which did not recognize the -339 to -316 target sequence when added alone, supershifted the mobility of in vitro translated C/EBP-α and C/EBP-β proteins complexed with the identified cis-regulatory element. These findings support the idea that heterodimerization between JUN and C/EBP-α and/or C/EBP-β targets JUN to the Sftpb promoter, thereby mediating its inhibitory regulatory role.

Effect of L-arginine on pulmonary surfactant in the rats with LPS-induced acute lung injury

Objectiye To investigate the effect of L-arginine on pulmonary surfactant (PS) in the rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods Forty-eight adult male SD rats weighing 220-270 g were randomly divided into 4 groups:group Ⅰ control (group C);group Ⅱ LPS;group Ⅲ LPS 3 h + L-arginine(group L1);group Ⅳ LPS6 h + L-arginine(group L2). ALI was induced by intravenous (Ⅳ)LPS 5 mg/kg in LPS,L1 and L2 groups. L-arginine 500 mg/kg was given intraperitoneally at 3 or 6 h after LPS administration in group L1 or group L2. The animals were sacrificed at 3 h after L-arginine administration, eight animals were sacrificed at 6 h and 9 h after LPS in group C and group LPS. The lungs were immediately removed for determination of surfactant-protein (SP-A) mRNA expression and broncho-alveolar lavage fluid (BALF). The total phospholipid (TPL) and total protein (TP) concentrations in the BALF were measured. Results SP-A mRNA in the lung tissue and TPL concentration in BALF were significantly decreased while TP concentration in BALF was significantly increased in group LPS, as compared with control groups( P ＜ 0.01 ). L-arginine given at 3 h after LPS administration significantly attenuated the LPS-induced changes while L-arginine given at 6 h after LPS did not. Conclusion L-arginine can protect the lungs from LPS-induced injury by up-regulating PS-expression. Key words: Arginine; Endotoxemia; Respiratory distress syndrome, adult; Pulmonary surfactantassociated proteins

Construction of eukaryote expression vector carrying human pulmonary surfactant-associated protein C and its expression in vitro

To clone human pulmonary surfactant-associated protein C (SP-C) and construct an eukaryote expression vector pcDNA3.1(+)/SP-C, and then to examine the SP-C expression in vitro, which may provide a reliable way of massive production of SP-C. The total RNA of normal lung tissue neighboring lung cancer from patients undergoing operation was extracted, and SP-C cDNA was then obtained by reverse transcription-polymerase chain reaction (RT-PCR). Both SP-C cDNA sequence and plasmid pcDNA3.1(+) were digested with NotI and XhoI, then connected by T4 DNA ligase after recycling agarose. After identification by restriction analysis and DNA sequencing, the recombinant was transfected into human breast cancer MCF-7 cells by using lipofectin reagent, and then the expression of SP-C was examined by RT-PCR and Western blotting. Human SP-C cDNA could be correctly cloned into the plasmid pcDNA3.1(+), and SP-C protein may be expressed in MCF-7 cells after transfection. By in vitro recombination, the eukaryote expression vector pcDNA3.1(+)/SP-C was successfully constructed and expressed SP-C in vitro, which rendered preparation for the construction of specific expression vector of human SP-C, and it laid the foundation of massive production of SP-C through mammary gland bioreactor.

A label-free differential proteomic analysis of mouse bronchoalveolar lavage fluid exposed to ultrafine carbon black

Ultrafine carbon black (ufCB) is a potential hazard to the lung. It causes changes in protein expression and it increases alveolar–capillary permeability in the lung. Label-free quantitative proteomic methods allow a sensitive and accurate analytical method for identifying and quantifying proteins in a protein mixture without chemically modifying the proteins. We used a label-free quantitative proteomic approach that combined and aligned LC–MS and LC–MS/MS spectra to analyze mouse bronchoalveolar lavage fluid (BALF) protein changes associated with exposure to ufCB. We developed a simple normalization method for quantification without spiking the internal standard. The intensities of unchanged peptides were used as normalization factors based on a statistical method to avoid the influence of peptides changed because of ufCB. LC–MS/MS spectra and then database searching were used to identify proteins. The relative abundances of the aligned peptides of identified proteins were determined using LC–MS spectra. We identified 132 proteins, of which 77 are reported for the first time. In addition, the expression of 15 inflammatory proteins and surfactant-associated proteins was regulated (i.e., 7 upregulated and 8 downregulated) compared with the controls. Several proteins not previously reported provide complementary information on the proteins present in mouse BALF, and they are potential biomarkers for the understanding of mechanisms involved in ufCB-induced lung disorders hypothesize that using the label-free quantitative proteomic approach introduced here is well suited for more rigorous, large-scale quantitative analysis of biological samples. We hypothesize that this label-free quantitative proteomic approach will be suited for a large-scale quantitative analysis of biological samples.

Review: Collectins link innate and adaptive immunity in allergic airway disease

Although the lipoprotein complex of pulmonary surfactant has long been recognized as essential for reducing lung surface tension, its role in lung immune host defense has only relatively recently been elucidated. Surfactant-associated proteins A (SP-A) and D (SP-D) can attenuate bacterial and viral infection and inflammation by acting as opsonins and by regulating innate immune cell functions. Surfactant-associated protein A and D also interact with antigen-presenting cells and T cells, thereby linking the innate and adaptive immune systems. A recent study from our laboratory demonstrated that mice deficient in SP-A have enhanced susceptibility to airway hyper-responsiveness and lung inflammation induced by Mycoplasma pneumonia, an atypical bacterium present in the airways of approximately 50% of asthmatics experiencing their first episode, and further supports an important role for SP-A in the host response to allergic airway disease. Animal and human studies suggest that alterations in the functions or levels of SP-A and SP-D are associated with both infectious and non-infectious chronic lung diseases such as asthma. Future studies are needed to elucidate whether alterations in SP-A and SP-D are a consequence and/or cause of allergic airway disease.

Effects of different ventilation modes on efficacy of exogenous pulmonary surfactant for treatment of rats with ventilator-induced lung injury

Objectlve To investigate the effects of different ventilation modes on the efficacy of exogenous pulmonary surfactant(PS)for the treatment of rats with ventilator-induced lung injury(VILI).Methods Forty-two male Wistar rats weighing 310-356 g were randomly divided into 6 groups(n=7 each):group CVT6,group SVT6,group CVT10,group SVT10,group CVT14 and group SVT14.The tidal volume(VT)was set at 6,10 and 14 ml/kg respectively and the respiratory rate(RR) was 75,45 and 32 bpm respectively.The animals were anesthetized with intraperitoneal 3% Pentobarbital 50 mg/kg,then tracheostomized and intubated.VILI model was induced by high-pressure ventilation (HPV) with peak inspimtory pressure (PIP) 40 cm H2O and without positive end-expiratory pressure (PEEP).The air was injected into the trachea via the airway at the end ofexpiration before HPV (T0,baseline value) and 15-25 min of HPV,the airway pressure monitored and the lung compliance(C) calculated.When C was decreased to half of the baseline value,PEEP was increased to 7.5 cm H20.After the tracheal edema fluid was removed,the PS 100 mg/kg was immediately injected into the trachea in group SVT6,SVT10 and SVT14.The equal volume of air was injected into the trachea in group CVT6,CVT10 and CVr14 instead of PS.Then the rats in different groups were ventilated with the corresponding ventilation modes.MAP was monitored and blood samples were token from femoral artery for blood gas analysis at T0, 5 min after HPV (T1 ), and 15, 30, 60, 90, 120 min (T2-6) after administration of PS. The tracheal edema fluid was collected at T1 and T6.The rats were killed at T6 and the lung tissues taken for microscopic examination. Results With the same ventilation mode, the VILI was significantly alleviated after administration of PS. With different ventilation modes,the lung injury was significantly reduced in group SVT 10 compared with the other groups. Conclusion The efficacy of PS for the treatment of rats with VILI is good using the ventilation strategy with VT of 10 ml/kg and RR of 45 bpm. Key words: Pulmonary surfactant-associated protein B; Pulmonary surfactant-associated protein C; Respiratory distress syndrome, adult; Respiration, artificial

Review: The intersection of surfactant homeostasis and innate host defense of the lung: lessons from newborn infants

The study of pulmonary surfactant, directed towards prevention and treatment of respiratory distress syndrome in preterm infants, led to the identification of novel proteins/genes that determine the synthesis, packaging, secretion, function, and catabolism of alveolar surfactant. The surfactant proteins, SP-A, SP-B, SP-C, and SP-D, and the surfactant lipid associated transporter, ABCA3, play critical roles in surfactant homeostasis. The study of their structure and function provided insight into a system that integrates the biophysical need to reduce surface tension in the alveoli and the innate host defenses required to maintain pulmonary structure and function after birth. Alveolar homeostasis depends on the intrinsic, multifunctional structures of the surfactant-associated proteins and the shared transcriptional regulatory modules that determine both the expression of genes involved in surfactant production as well as those critical for host defense. Identification of the surfactant proteins and the elucidation of the genetic networks regulating alveolar homeostasis have provided the basis for understanding and diagnosing rare and common pulmonary disorders, including respiratory distress syndrome, inherited disorders of surfactant homeostasis, and pulmonary alveolar proteinosis.

Loss of βarrestin1 and βarrestin2 contributes to pulmonary hypoplasia and neonatal lethality in mice

Less is known about the connection between the malfunction of βarrestins and developmental defects as the mice with either of two βarrestin isoforms knockout appear normal. In order to address the biological function of βarrestins during developmental process, we generate βarrestin1/2 double knockout mice. We found that βarrestin1/2 dual-null mice developed respiratory distress and atelectasis that subsequently caused neonatal death. Morphological examination revealed type II pneumocyte immaturity. Our results indicate that not only βarrestin1/2 double knockout lung tissue show disturbances in cell proliferation but βarrestin1 and βarrestin2 contribute to pulmonary surfactant complex generation during pulmonary maturation. Intra-amniotic delivery of recombinant adenovirus expressing βarrestin1 or βarrestin2 enhances surfactant-associated proteins synthesis in vivo. Our mRNA microarray data further reveal that βarrestin1/2 double knockout results in downregulation of a significant proportion of genes involved in several lung morphogenesis processes. Together, our study demonstrates that βarrestin1 and βarrestin2 collaborate in embryonic development processes for epithelial pneumocyte differentiation and lung maturation.

Effects of positive end expiratory pressure ventilation upon respiratory function and hydrophobic surfactants proteins in rabbit with seawater respiratory distress syndrome

To investigate the effects of positive end-expiratory pressure (PEEP) ventilation upon respiratory function and lung surfactant protein B (SP-B)/SP-C in seawater respiratory distress syndrome (SW-RDS) rabbit. Twenty-four female New Zealand rabbits were randomly equally divided into three groups:conventional mechanical ventilation (CMV) group, PEEP group, and control group. After anesthesia and tracheal intubation followed by 20 minutes of CMV, SW-RDS model was established by lung perfusion of artificial seawater through tracheal intubation. Then the CMV group ventilated for 6 hours (each parameter unchanged); PEEP group ventilated with PEEP of 8 cm H2O for 2 hours based on prior parameters and subsequently with CMV for 4 hours; control group without ventilation after modeling. Oxygenation indices and lung compliance were continuously monitored during ventilation. After ventilation, the rabbits in study groups were sacrificed while those dying a natural death in the control group selected. Bronchoalveolar lavage fluid of the left lung was collected to determine the alveolar surface tension and the right lung was harvested to measure the mRNA expression of SP-B/SP-C by real-time PCR as well as SP-B protein by Western blotting. After modeling, the data of lung compliance and oxygenation indices became significantly worse in every group but without statistical difference in three groups. All rabbits in control group died within 15 minutes of ventilator withdrawal. After receiving PEEP ventilation for 30 minutes, these indices significantly improved compared with CMV group in which there was no significant change of the indices (P < 0.05). Minimal alveolar surface tension in CMV group (mN/m, 30.8 +/- 6.3) was greater than in PEEP group (21.1 +/- 4.4, P < 0.05) and control group (23.6 +/- 4.6, P < 0.05); SP-B/SP-C mRNA relative expression (0.37 +/- 0.15/0.60 +/- 0.19) and SP-B relative protein abundance (0.38 +/- 0.17) in CMV group were obviously lower than in PEEP group (0.73 +/- 0.15/0.92 +/- 0.40, 0.52 +/- 0.22, P < 0.05). PEEP ventilation can improve the oxygenation indices and lung compliance in SW-RDS animals. And such an effect is correlated with both the mRNA expressions of SP-B/SP-C and mechanical distension.

Lung surfactant proteins in the early human placenta

Pulmonary surfactant is a complex mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C and SP-D). The biological functions of SP-A and SP-D are primarily twofold, namely surfactant homeostasis and host defense. The hydrophobic surfactant proteins, SP-B and SP-C, are required for achieving the optimal surface tension reducing properties of surfactant by promoting the rapid adsorption of surfactant phospholipids along the alveolar surface. Despite the promising findings, only little is known about the extrapulmonary distribution of these proteins. Therefore, in this study, the presence of SP-A, SP-B, SP-C and SP-D in early human placenta has been investigated. First-trimester placental tissues (22-56 days) were obtained from women undergoing curettage during normal pregnancies. In parallel tissue sections, vimentin, cytokeratin-7 and CD-68 immunostainings were used for the identification of mesenchymal cells, trophoblast cells and Hofbauer cells, respectively. According to immunohistochemistry (IHC) results, SP-A, SP-B, SP-C and SP-D immunoreactivities with different staining intensities were observed in trophoblastic layers of chorionic villous tree, trophoblastic cell columns, stromal cells, Hofbauer cells, angiogenic cell cords and vascular endothelium. Fetal hematopoietic cells showed a variable staining pattern for all four surfactant proteins ranging from none to strong intensity. Western blotting of tissue extracts confirmed our IHC results. The presence of surfactant glycoproteins in early human placenta may yield a very important feature of surfactants during first trimester and enables further studies of the role of surfactants in various pregnancy complications.