Surfactant Secretion Research Articles

Tracing exogenous surfactant in vivo in rabbits by the natural variation of 13C

BackgroundRespiratory Distress Syndrome (RDS) is a prematurity-related breathing disorder caused by a quantitative deficiency of pulmonary surfactant. Surfactant replacement therapy is effective for RDS newborns, although treatment failure has been reported. The aim of this study is to trace exogenous surfactant by 13C variation and estimate the amount reaching the lungs at different doses of the drug.MethodsForty-four surfactant-depleted rabbits were obtained by serial bronchoalveolar lavages (BALs), that were merged into a pool (BAL pool) for each animal. Rabbits were in nasal continuous positive airway pressure and treated with 0, 25, 50, 100 or 200 mg/kg of poractant alfa by InSurE. After 90 min, rabbits were depleted again and a new pool (BAL end experiment) was collected. Disaturated-phosphatidylcholine (DSPC) was measured by gas chromatography. DSPC-Palmitic acid (PA) 13C/12C was analyzed by isotope ratio mass spectrometry. One-way non-parametric ANOVA and post-hoc Dunn’s multiple comparison were used to assess differences among experimental groups.ResultsBased on DSPC-PA 13C/12C in BAL pool and BAL end experiment, the estimated amount of exogenous surfactant ranged from 61 to 87% in dose-dependent way (p < 0.0001) in animals treated with 25 up to 200 mg/kg. Surfactant administration stimulated endogenous surfactant secretion. The percentage of drug recovered from lungs did not depend on the administered dose and accounted for 31% [24–40] of dose.ConclusionsWe reported a risk-free method to trace exogenous surfactant in vivo. It could be a valuable tool for assessing, alongside the physiological response, the delivery efficiency of surfactant administration techniques.

In Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2 Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids

(Stem Cell Reports 12, 431–440; March 5, 2019) In the originally published version of our manuscript, the legend to Figure S3 in the Supplemental Information was accidentally removed during the proofing process. To address this, we have now replaced the Supplemental Information with the correct version. We apologize for the oversight and for any resulting confusion. In Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2 Using Human Induced Pluripotent Stem Cell-Derived Alveolar OrganoidsKorogi et al.Stem Cell ReportsFebruary 14, 2019In BriefPulmonary surfactant secretion by alveolar type 2 (AT2) cells is crucial for alveolar homeostasis. Gotoh and colleagues generated Hermansky-Pudlak syndrome type 2 (HPS2) patient-derived iPSCs and their gene-corrected counterparts and differentiated them into alveolar organoids (AOs). In HPS2-AOs, aberrant lamellar bodies and impaired surfactant secretion were demonstrated. Human iPSC-derived AOs might be useful for investigating alveolar lung diseases. Full-Text PDF Open Access

Spatiotemporal Dynamics of Molecular Messaging in Bacterial Co-Cultures Studied by Multimodal Chemical Imaging.

Microbial community behavior is coupled to a set of genetically-regulated chemical signals that correlate with cell density - the quorum sensing (QS) system - and there is growing appreciation that the QS-regulated behavior of bacteria is chemically, spatially, and temporally complex. In addition, while it has been known for some time that different species use different QS networks, we are beginning to appreciate that different strains of the same bacterial species also differ in their QS networks. Here we combine mass spectrometric imaging (MSI) and confocal Raman microscopy (CRM) approaches to investigate co-cultures involving different strains (FRD1 and PAO1C) of the same species (Pseudomonas aeruginosa) as well as those involving different species (P. aeruginosa and E. coli). Combining MSI and CRM makes it possible to supersede the limits imposed by individual imaging approaches and enables the spatial mapping of individual bacterial species and their microbial products within a mixed bacterial community growing in situ on surfaces. MSI is used to delineate the secretion of a specific rhamnolipid surfactant as well as alkyl quinolone (AQ) messengers between FRD1 and PAO1C strains of P. aeruginosa, showing that the spatial distribution and production rate of AQ messengers in PAO1C far outstrips that of FRD1. In the case of multiple species, CRM is used to show that the prolific secretion of AQs by the PAO1C strain of P. aeruginosa is used to mediate its interaction with co-cultured E. coli.

Dead space ventilation promotes alveolar hypocapnia reducing surfactant secretion by altering mitochondrial function

BackgroundIn acute respiratory distress syndrome (ARDS), pulmonary perfusion failure increases physiologic dead space ventilation (VD/VT), leading to a decline of the alveolar CO2 concentration [CO2]iA. Although it has been shown...

Foetal Development in Mammals

During the fetal period are carried out a series of necessary changes, which prepare the fetus for extrauterine life, culminating embryonic development, leading to this physiological maturation of tissues, organs and systems, along with a rapidly growing body. Well being bought, the species-specific features. Other events of interest are beginning the process of ossification of the bones (short and long), formation of the eyelids; integumentary and other elements besides the surfactant secretion from lungs. In this paper we will make a description of the main events that characterized this period, along with a comparison of them among some domestic mammals.

Exposure to diethylhexyl phthalate (DEHP) and monoethylhexyl phthalate (MEHP) promotes the loss of alveolar epithelial phenotype of A549 cells

Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that is metabolized to mono(2-ethylhexyl) phthalate (MEHP). Inhalation is an important exposure route for both phthalates, and their effects on lungs include inflammation, alteration of postnatal maturation (alveolarization), enlarged airspaces and cell differentiation changes, suggesting that alveolar epithelial cells-2 (AEC) are targets of phthalates. This study evaluated the cell progression, epithelial and mesenchymal markers, including surfactant secretion in A549 cells (AEC) that were exposed to DEHP (1–100 μM) or MEHP (1–50 μM) for 24–72 h. The results showed an increased cell proliferation at all concentrations of each phthalate at 24 and 48 h. Cell migration showed a concentration-dependent increase at 24 and 48 h of exposure to either phthalate and enlarged structures were seen. Decreased levels of both surfactants (SP-B/SP-C) were observed after the exposure to either phthalate at 48 h, and of SP-C positive cells exposed to MEHP, suggesting a loss of the epithelial phenotype. While a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal marker fibronectin were observed following exposure to either phthalate. Our results showed that DEHP and MEHP altered the structure and migration of A549 cells and promoted the loss of the epithelial phenotype.

7 powodów, dla których warto stosować ambroksol

Ambroxol is a broad-spectrum mucokinetic drug. It occurs in the oral, parenteral and inhalation form. This drug stimulates the synthesis and secretion of surfactant, has anti-inflammatory, antioxidant and antiviral properties. The paper discusses 7 reasons why ambroxol should be used in children.

Pulmonary surfactant protein SP‐B promotes exocytosis of lamellar bodies in alveolar type II cells

The release of pulmonary surfactant by alveolar type II (ATII) cells is essential for lowering surface tension at the respiratory air-liquid interface, stabilizing the lungs against physical forces tending to alveolar collapse. Hydrophobic surfactant protein (SP)-B ensures the proper packing of newly synthesized surfactant particles, promotes the formation of the surface active film at the alveolar air-liquid interface and maintains its proper structure along the respiratory dynamics. We report that membrane-associated SP-B efficiently induces secretion of pulmonary surfactant by ATII cells, at the same level as potent secretagogues such as ATP. The presence in the extracellular medium of lipid-protein complexes containing SP-B activates the P2Y2 purinergic signaling pathway that ultimately triggers exocytosis of lamellar bodies by ATII cells. Our data suggest that SP-B prompts Ca2+-dependent surfactant secretion via ATP release from ATII cells. This result implies that SP-B is not only an essential component for the biophysical function of surfactant but is also a central element in the alveolar homeostasis by eliciting autocrine and paracrine cell stimulation.-Martínez-Calle, M., Olmeda, B., Dietl, P., Frick, M., Pérez-Gil, J. Pulmonary surfactant protein SP-B promotes exocytosis of lamellar bodies in alveolar type II cells.

Characteristics of surfactant proteins in tumorigenic and inflammatory lung lesions in rodents.

Surfactant proteins (SPs) are essential for the proper structure and respiratory function of the lungs. There are four subtypes of SPs: SP-A, SP-B, SP-C, and SP-D. The expectorant drug ambroxol hydrochloride is clinically used to stimulate pulmonary surfactant and airway serous secretion. In addition, previous studies showed that ambroxol regulated SP production and attenuated pulmonary inflammation, with ambroxol hydrochloride being found to suppress quartz-induced lung inflammation via stimulation of pulmonary surfactant and airway serous secretion. In this study, we investigated the expression of SP-A, SP-B, SP-C, and SP-D in neoplastic and inflammatory lung lesions in rodents, as well as their possible application as potential markers for diagnostic purposes. SP-B and SP-C showed strong expression in lung hyperplasia and adenoma, whereas SP-A and SP-D were expressed in the mucus or exudates of inflammatory alveoli. Rodent tumorigenic hyperplasic tissues induced by various carcinogens were positive for napsin A, an aspartic proteinase involved in the maturation of SP-B; this indicated a focal increase in type II pneumocytes in the lungs. Therefore, high expression of napsin A in the alveolar walls may serve as a useful marker for prediction of the tumorigenic potential of lung hyperplasia in rodents.

The Influence of BuqiHuoxueTongluo Formula on Histopathology and Pulmonary Function Test in Bleomycin-Induced Idiopathic Pulmonary Fibrosis in Rats.

BuqiHuoxueTongluo Formula (BHTF) is an effective herbal prescription based on traditional Chinese medicine for idiopathic pulmonary fibrosis (IPF). The aim of this study was to elucidate the influence of BHTF on induced IPF model through the aspect of histopathology and pulmonary function test. Wistar rats with bleomycin-induced IPF were given BHTF via intragastric gavage. After 14 days and 28 days of treatment, respectively, on these two time points, we first performed pulmonary function test, performed ventilation measure, and traced the Pressure-Volume Loop under anesthesia. Then, rats were sacrificed for hematoxylin-eosin and Masson's trichrome staining, immunohistochemistry staining of TGF-β1 and α-SMA, and observation through transmission electron microscope. BHTF reduced infiltration of inflammation cells, collagen deposition, and fibrosis proliferation in pulmonary mesenchyme, inhibited the expression of TGF-β1 and α-SMA, and avoided the abnormality of ultrastructure and quantities of lamellar bodies. It also ameliorated the parameters of FVC, MVV, PEF, FEF25, and Cdyn, maintained the shape of the Pressure-Volume Loop, and improved hysteresis. BHFT relieved the histopathologic changes, improved ventilation function, compliance, and work of breathing, meliorated the capacity and elasticity of the lungs, and stabilized the alveolar surface tension. Further speaking, it had a potential impact on the secretion of pulmonary surfactant.

Effects of the expectorant drug ambroxol hydrochloride on chemically induced lung inflammatory and neoplastic lesions in rodents.

Ambroxol hydrochloride (AH) is an expectorant drug used to stimulate pulmonary surfactant and serous airway secretion. Surfactant proteins (SPs) are essential for maintaining respiratory structure and function, although SP expression has also been reported in lung inflammatory and proliferative lesions. To determine whether AH exerts modulatory effects on these lung lesions, we examined its effects on pleural thickening induced by intrathoracic administration of dipotassium titanate (TISMO) in A/JJmsSlc (A/J) mice. We also analyzed the modulatory effects of AH on neoplastic lung lesions induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice and by N-nitrosobis (2-hydroxypropyl) amine (DHPN) in F344/DuCrlCrj (F344) rats. A/J mice treated with TISMO showed decreased body weight, increased white blood cell (WBC) counts, and pleural thickening caused by pleuritis and poor general condition. However, A/J mice treated with TISMO + 120 ppm showed significant recovery of body weight and WBC counts to the same levels as those of A/J mice not treated with TISMO, although no significant differences were observed in histopathological changes including the immunohistopathological expression of IL-1β in the lung and maximum pleural thickness regardless of AH treatment. In the NNK and DHPN experiments, no significant differences in body weight, hematology, plasma biochemistry, and histopathological changes were associated with AH concentration. These results suggest that AH potentially exerts anti-inflammatory effects but does not have a direct suppressive effect on lung tumorigenesis in rodents.

ATP is stored in lamellar bodies to activate vesicular P2X4 in an autocrine fashion upon exocytosis.

Vesicular P2X4 receptors are known to facilitate secretion and activation of pulmonary surfactant in the alveoli of the lungs. P2X4 receptors are expressed in the membrane of lamellar bodies (LBs), large secretory lysosomes that store lung surfactant in alveolar type II epithelial cells, and become inserted into the plasma membrane after exocytosis. Subsequent activation of P2X4 receptors by adenosine triphosphate (ATP) results in local fusion-activated cation entry (FACE), facilitating fusion pore dilation, surfactant secretion, and surfactant activation. Despite the importance of ATP in the alveoli, and hence lung function, the origin of ATP in the alveoli is still elusive. In this study, we demonstrate that ATP is stored within LBs themselves at a concentration of ∼1.9 mM. ATP is loaded into LBs by the vesicular nucleotide transporter but does not activate P2X4 receptors because of the low intraluminal pH (5.5). However, the rise in intravesicular pH after opening of the exocytic fusion pore results in immediate activation of vesicular P2X4 by vesicular ATP. Our data suggest a new model in which agonist (ATP) and receptor (P2X4) are located in the same intracellular compartment (LB), protected from premature degradation (ATP) and activation (P2X4), and ideally placed to ensure coordinated and timely receptor activation as soon as fusion occurs to facilitate surfactant secretion.

Alveolar injury and regeneration following deletion of ABCA3.

Adaptation to air breathing after birth is dependent upon the synthesis and secretion of pulmonary surfactant by alveolar type 2 (AT2) cells. Surfactant, a complex mixture of phospholipids and proteins, is secreted into the alveolus, where it reduces collapsing forces at the air-liquid interface to maintain lung volumes during the ventilatory cycle. ABCA3, an ATP-dependent Walker domain containing transport protein, is required for surfactant synthesis and lung function at birth. Mutations in ABCA3 cause severe surfactant deficiency and respiratory failure in newborn infants. We conditionally deleted the Abca3 gene in AT2 cells in the mature mouse lung. Loss of ABCA3 caused alveolar cell injury and respiratory failure. ABCA3-related lung dysfunction was associated with surfactant deficiency, inflammation, and alveolar-capillary leak. Extensive but incomplete deletion of ABCA3 caused alveolar injury and inflammation, and it initiated proliferation of progenitor cells, restoring ABCA3 expression, lung structure, and function. M2-like macrophages were recruited to sites of AT2 cell proliferation during the regenerative process and were present in lung tissue from patients with severe lung disease caused by mutations in ABCA3. The remarkable and selective regeneration of ABCA3-sufficient AT2 progenitor cells provides plausible approaches for future correction of ABCA3 and other genetic disorders associated with surfactant deficiency and acute interstitial lung disease.

Pulmonary alveolar proteinosis, unusual infiltrative lung disease, the dilemma for physicians: A case report and literature review

Introduction: Pulmonary alveolar proteinosis (PAP) is a diffuse pulmonary disease characterized by the intra-alveolar accumulation of formless, proteinaceous material. Lipids and proteins materials with specific staining appearance in the alveoli impair pulmonary gas transfer in PAP. The severity of this condition ranges from an asymptomatic clinical presentation to respiratory failure and death. PAP is an extremely rare disorder, occurring worldwide with an estimated prevalence of 0.1 per 100000 individuals. Although the pathogenesis of PAP has remained unknown, most investigators have considered this condition to be caused by the impaired clearance of lipids and surfactant proteins from the airspaces. These functions are known to be performed by alveolar macrophages and type 2 epithelial cells. It is likely that granulocyte macrophage-colony stimulating factor (GM-CSF) dysfunction on macrophages is responsible for PAP. Primarily, in most adult patients with PAP, antibodies against GM-CSF have been observed with dysfunction of macrophages. Secondly, alveolar macrophage dysfunction plays a role in the impaired secretion of surfactant in this disease. It has been noted that both impaired secretion of surfactant and impaired phagocytosis are responsible for disease pathogenesis. Case Report: A 40-year-old man who had suffered from a cough with sputum for more than 2 years, with no associated fever, referred to our clinic. He had been diagnosed with pneumonia and treated unsuccessfully with antibiotics. His past medical history showed that he had a chronic history of a cough, easy fatigability and shortness of breath upon mild exertion. Computed tomography (CT) imaging of the chest revealed bilateral diffuse reticulonodular opacities and a crazy-paving pattern, which was suggestive of alveolar proteinosis. Conclusion: PAP is a generalized pulmonary disorder caused by the collection of formless, proteinaceous material with specific staining appearance in the alveolus.

Functional roles of C/EBPα and SUMO‑modification in lung development.

CCAAT enhancer binding protein alpha (C/EBPα) is a transcription factor regulating the core aspects of cell growth and differentiation. The present study investigated the level and functional role of C/EBPα during the development of the rat lung. C/EBPα protein exhibits a dynamic expression pattern. The correlation between the expression of C/EBPα protein and the content of glycogen during lung maturation was analyzed to understand the function of C/EBPα in lung differentiation. The high expression of C/EBPα coincides with the reduction of glycogen in the fetal lung. In addition, the authors identified that changes in the level of C/EBPα are associated with the secretion of pulmonary surfactant. C/EBPα is modified by small ubiquitin-related modifier (SUMO) post-translationally. The results of double immunofluorescence staining and immunoprecipitation demonstrated that SUMO-modified C/EBPα was present in the lung. The sumoylated C/EBPα gradually decreased during lung differentiation and was negatively correlated with pulmonary surfactant secretion, thereby suggesting that the SUMO modification may participate in C/EBPα-mediated lung growth and differentiation. These results indicated that C/EBPα played a role in lung development and provided the insight into the mechanism underlying SUMO-modification.

Adenovirus vector expressing keratinocyte growth factor using CAG promoter impairs pulmonary function of mice with elastase-induced emphysema.

Pulmonary emphysema impairs quality of life and increases mortality. It has previously been shown that administration of adenovirus vector expressing murine keratinocyte growth factor (KGF) before elastase instillation prevents pulmonary emphysema in mice. We therefore hypothesized that therapeutic administration of KGF would restore damage to lungs caused by elastase instillation and thus improve pulmonary function in an animal model. KGF expressing adenovirus vector, which prevented bleomycin-induced pulmonary fibrosis in a previous study, was constructed. Adenovirus vector (1.0 × 109 plaque-forming units) was administered intratracheally one week after administration of elastase into mouse lungs. One week after administration of KGF-vector, exercise tolerance testing and blood gas analysis were performed, after which the lungs were removed under deep anesthesia. KGF-positive pneumocytes were more numerous, surfactant protein secretion in the airspace greater and mean linear intercept of lungs shorter in animals that had received KGF than in control animals. Unexpectedly, however, arterial blood oxygenation was worse in the KGF group and maximum running speed, an indicator of exercise capacity, had not improved after KGF in mice with elastase-induced emphysema, indicating that KGF-expressing adenovirus vector impaired pulmonary function in these mice. Notably, vector lacking KGF-expression unit did not induce such impairment, implying that the KGF expression unit itself may cause the damage to alveolar cells. Possible involvement of the CAG promoter used for KGF expression in impairing pulmonary function is discussed.

Misoprostol before Elective Caesarean Section for Decreasing the Neonatal Respiratory Morbidity : A Randomized Control Trial

Background: neonatal respiratory morbidities are common neonatal outcome the worrisome the mothers the most when approaching labour. They vary in clinical presentations with various long term effects, the most importantly related to caesarean section are Transient Tachypnea of the Newborn (TTN), Respiratory Distress Syndrome (RDS), Persistent Pulmonary Hypertension (PPHN). Aim of the Work: the aim of this study is to assess the efficacy of Misoprostol or the Prostaglandin E1( PGE1) on the reduction of the neonatal respiratory morbidity in women scheduled for term caesarean section (38-38+6 weeks Gestational Age (GA). Patients and Methods: this is a Randomized Controlled Trial (RCT) which was conducted over six months from November 2016, to April 2017 on 120 pregnant women who were approached before elective caesarean section (ECS), managed in Ain Shams University Maternity Hospital (ASUMH), and their neonates followed up in the Neonatal Intensive Care Unit (NICU) of Ain Shams University Maternity Hospital to assess the effect of Misoprostol when given for women one hour before their scheduled caesarean section upon reducing the neonatal respiratory morbidity. Results: the current study revealed a highly statistically significant difference between groups according to respiratory morbidity, and especially the TTN using Chi-square test, with p-value <0.001 Highly Significant. Conclusion: the study concluded that when a vaginal tab containing Misoprostol 200 microgram given to women one hour before term elective caesarean section between 38-38+6 weeks compared to placebo, it simulates the normal labour to enable the neonate through catecholamines surge, and thus surfactant secretion for better adaptation to the extrauterine life. Recommendations: Misoprostol can be administered vaginally to candidate pregnant women with term pregnancies with certain inclusion criteria before an elective caesarean section (after exclusion of any contraindication and thorough good history taking and clinical examination) in order to reduce the neonatal respiratory morbidity and especially the transient tachypnea of newborn. Thus, decrease the duration of neonatal NICU admission and mortality.

Transcriptomic profiling reveals disordered regulation of surfactant homeostasis in neonatal cloned bovines with collapsed lungs and respiratory distress.

Respiratory distress is a major cause of mortality in cloned neonatal animals, but its pathogenesis remains poorly understood. Here, we used necropsy and histology procedures to evaluate the lungs of cloned neonatal bovines dying of respiratory distress, finding incomplete lung dilation, alveolar collapse, and thickened alveolar walls. Comparison of the transcriptomes between collapsed lungs of cloned bovines and their normal counterparts revealed 1373 differentially expressed genes in collapsed lungs (p < 0.05, fold change >1.5 or <1.5-1 ), many of which were associated with surfactant biosynthesis, secretion, transport, recycling, and degradation. ERK/MAPK and Notch signaling pathways were among the canonical pathways relevant to surfactant homeostasis. Expression of the genes encoding Surfactant protein B (SPB) and Surfactant protein C (SPC)-which control surfactant lipid packing, spreading, and stability-were significantly lower in collapsed lungs of cloned neonates at the transcript (p < 0.01) and protein levels (p < 0.05) relative to that in normal lungs. Thus, our results provide an initial view into the changes in gene expression in cloned newborns with lung collapse and respiratory distress, and present a valuable resource for developing novel preventive or therapeutic strategies to reduce the mortality rate of cloned animals and to improve the efficiency of somatic cell nuclear transfer technology.

Epithelial Gpr116 regulates pulmonary alveolar homeostasis via Gq/11 signaling.

Pulmonary function is dependent upon the precise regulation of alveolar surfactant. Alterations in pulmonary surfactant concentrations or function impair ventilation and cause tissue injury. Identification of the molecular pathways that sense and regulate endogenous alveolar surfactant concentrations, coupled with the ability to pharmacologically modulate them both positively and negatively, would be a major therapeutic advance for patients with acute and chronic lung diseases caused by disruption of surfactant homeostasis. The orphan adhesion GPCR GPR116 (also known as Adgrf5) is a critical regulator of alveolar surfactant concentrations. Here, we show that human and mouse GPR116 control surfactant secretion and reuptake in alveolar type II (AT2) cells by regulating guanine nucleotide-binding domain α q and 11 (Gq/11) signaling. Synthetic peptides derived from the ectodomain of GPR116 activated Gq/11-dependent inositol phosphate conversion, calcium mobilization, and cortical F-actin stabilization to inhibit surfactant secretion. AT2 cell-specific deletion of Gnaq and Gna11 phenocopied the accumulation of surfactant observed in Gpr116-/- mice. These data provide proof of concept that GPR116 is a plausible therapeutic target to modulate endogenous alveolar surfactant pools to treat pulmonary diseases associated with surfactant dysfunction.

Natriuretic peptide C receptor in the developing sheep lung: role in perinatal transition

Background: At birth, the release of surfactant from alveolar type II cells (ATIIs) is stimulated by increased activity of the beta-adrenergic/adenylyl cyclase/cyclic 3'-5' adenosine monophosphate-signaling cascade. Atrial natriuretic peptide (ANP) stimulates surfactant secretion through natriuretic peptide receptor A (NPR-A). ANP inhibits adenylyl cyclase activity through its binding to NPR-C. We wished to further understand the role of the NPR-C in perinatal transition. Methods: We studied ATII expression of NPR-C in fetal and newborn sheep using immunohistochemistry, and surfactant secretion in isolated ATIIs by measuring 3[H] choline release into the media. Results: ANP induced surfactant secretion, and, at higher doses, it inhibits the stimulatory effect of the secretagogue terbutaline. ATII NPR-C expression decreased significantly after birth. Premature delivery also markedly decreased ANP and NPR-C in ATIIs. Co-incubation of terbutaline (10-4 M) with ANP (10-6 M) significantly decreased 3[H] choline release from isolated newborn ATII cells when compared with terbutaline alone; this inhibitory effect was mimicked by the specific NPR-C agonist, C-ANP (10-10 M). Conclusion: ANP may act as an important epithelial-derived inhibitor of surfactant release in the fetal lung, and downregulation of ANP and NPR-C following birth may sensitize ATII cells to the effects of circulating catecholamines, thus facilitating surfactant secretion.