Dexamethasone and epinephrine stimulate surfactant secretion in type II cells of embryonic chickens

2001 ◽  
Vol 281 (3) ◽  
pp. R770-R777 ◽  
Author(s):  
Lucy C. Sullivan ◽  
Sandra Orgeig
Keyword(s):  
Lung Development ◽  
Pulmonary Surfactant ◽  
Egg Laying ◽  
Lung Fibroblasts ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lung Structure ◽  
Cellular Pathways ◽  
And Function

Pulmonary surfactant (PS), a mixture of phospholipids and proteins secreted by alveolar type II cells, functions to reduce the surface tension in the lungs of all air-breathing vertebrates. Here we examine the control of PS during lung development in a homeothermic egg-laying vertebrate. In mammals, glucocorticoids and autonomic neurotransmitters contribute to the maturation of the surfactant system. We examined whether dexamethasone, epinephrine, and carbamylcholine hydrochloride (agonist for acetylcholine) increased the amount of PS secreted from cultured type II cells of the developing chicken lung. In particular, we wanted to establish whether dexamethasone would increase PS secretion through a process involving lung fibroblasts. We isolated and cocultured type II cells and lung fibroblasts from chickens after 16, 18, and 20 days of incubation and from hatchlings ( day 21). Epinephrine stimulated phosphatidylcholine (PC) secretion at all stages, whereas dexamethasone stimulated secretion of PC at days 16 and 18. Carbamylcholine hydrochloride had no effect at any stage. This is the first study to establish the existence of similar cellular pathways regulating the development of surfactant in chickens and eutherian mammals, despite the vastly different birthing strategies and lung structure and function.

Requirements for extracellular metabolism of pulmonary surfactant: tentative identification of serine protease

1992 ◽  
Vol 262 (4) ◽  
pp. L446-L453 ◽  
Author(s):  
N. J. Gross ◽  
R. M. Schultz
Keyword(s):  
Serine Protease ◽  
Surface Area ◽  
Pulmonary Surfactant ◽  
Lamellar Body ◽  
Alveolar Epithelium ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Ph Optimum

Pulmonary alveolar surfactant is secreted by the alveolar epithelium in the form of lamellar bodylike structures that evolve sequentially into tubular myelin and vesicular forms that can be separated by centrifugation. Using an in vitro procedure by which the extracellular metabolism of pulmonary surfactant can be mimicked, namely cyclic variation in surface area, we previously reported that serine protease activity, which we called “convertase,” was required for the conversion of tubular myelin to the vesicular form. In the present studies we explored the biochemical requirements of this activity and sought the enzyme in alveolar products. Convertase activity has unusual requirements; in addition to being dependent on repetitive variations in surface area (cycling), it requires the presence of a high g fraction of lung secretions that is heat stable and not inhibitable by diisopropyl fluorophosphate (DFP) or alpha 1-antitrypsin, both typical serine protease inhibitors. The enzyme does not require calcium ions and has a pH optimum of 7.4. Convertase appears to be a component of surfactant itself because the ability of purified surfactant to convert to the vesicular form on cycling is impaired by pretreating it with DFP. A protein of Mr 75,000 that reacts with DFP and is heat sensitive was found in alveolar lavage, lamellar body preparations, and lung homogenate. It copurifies with lung surfactant in sucrose gradients. A similar DFP-reactive protein was observed in stable human neoplastic peripheral airway cell lines that express type II properties, suggesting that it may be a product of type II cells. We tentatively conclude that surfactant convertase is a 75,000 serine protease that is closely associated with surfactant phospholipid and that may be a product of alveolar type II cells.

Enhanced alveolar type II cell growth on a pulmonary extracellular matrix over fibroblasts

1997 ◽  
Vol 272 (3) ◽  
pp. L413-L417 ◽  
Author(s):  
I. Y. Adamson ◽  
L. Young ◽  
J. Bakowska
Keyword(s):  
Extracellular Matrix ◽  
Cell Growth ◽  
Growth Effect ◽  
Lung Fibroblasts ◽  
Cell Contact ◽  
Alveolar Type ◽  
Thymidine Uptake ◽  
Type Ii Cells ◽  
Type Ii ◽  
Type Ii Cell

The growth of alveolar type II cells was studied when these cells were maintained for 2 days on a pulmonary endothelium-derived extracellular matrix (ECM) on a filter with or without lung fibroblasts in the lower chambers of culture wells. Type II cell proliferation was enhanced by the ECM compared with other substrates but was significantly higher with fibroblasts beneath. This was determined by thymidine uptake and cell numbers. The diffusing factor from fibroblasts appeared to be keratinocyte growth factor (KGF), because this cytokine increased type II cell growth in culture and the neutralizing antibody to KGF blocked the observed fibroblast-induced growth increase. None of the antibodies to various cytokines had any effect on the ECM-induced proliferation. Although the type II cells were shown to produce degradative activity for the ECM, there was little secreted enzyme activity in supernatants and there was no demonstrated autocrine-regulated growth effect. The results suggest that type II cell growth may be stimulated by both 1) a matrix-bound factor that acts through a cell contact-mediated process, and 2) a fibroblast-secreted factor that appears to be KGF.

Pulmonary surfactant protein A-mediated uptake of phosphatidylcholine by alveolar type II cells

1993 ◽  
Vol 265 (2) ◽  
pp. L193-L199 ◽  
Author(s):  
A. Tsuzuki ◽  
Y. Kuroki ◽  
T. Akino
Keyword(s):  
Pulmonary Surfactant ◽  
Protein A ◽  
Lamellar Body ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lamellar Bodies ◽  
Pulmonary Surfactant Protein

Pulmonary surfactant protein A (SP-A)-mediated uptake of phosphatidylcholine (PC) by alveolar type II cells was investigated. SP-A enhanced the uptake of liposomes containing dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-linoleoyl phosphatidylcholine (PLPC), or 1,2-dihexadecyl-sn-glycero-3-phosphocholine (DPPC-ether), a diether analogue of DPPC, but about twice as much DPPC was taken up by type II cells as PLPC or DPPC-ether. When subcellular distribution was analyzed, 51.3 +/- 2.9% (mean +/- SD, n = 3) of cell-associated radiolabeled DPPC was recovered in the lamellar body-rich fraction in the presence of SP-A, whereas only 19.3 +/- 1.9% (mean +/- SD, n = 3) was found to this fraction in the absence of SP-A. When type II cells were incubated either with DPPC at 0 degree C or with DPPC-ether at 37 degrees C, or no cells were included, low proportions of the cell-associated lipids were present in the fractions corresponding to lamellar bodies even in the presence of SP-A. Anti-SP-A antibody significantly reduced the radioactivity incorporated into the lamellar body fraction. Phosphatidylcholine that had been incorporated into lamellar bodies remained largely intact when SP-A was present. Subcellular fractionations of type II cells with radiolabeled SP-A and DPPC revealed that the sedimentation characteristics of cell-associated SP-A are different from those of DPPC, although a small broad peak of radiolabeled SP-A was found in the lamellar body fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Transitional human alveolar type II epithelial cells suppress extracellular matrix and growth factor gene expression in lung fibroblasts

2019 ◽  
Vol 317 (2) ◽  
pp. L283-L294 ◽  
Author(s):  
Kelly A. Correll ◽  
Karen E. Edeen ◽  
Rachel L. Zemans ◽  
Elizabeth F. Redente ◽  
Karina A. Serban ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Surfactant Protein ◽  
Lung Fibroblasts ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
I Cells

Epithelial-fibroblast interactions are thought to be very important in the adult lung in response to injury, but the specifics of these interactions are not well defined. We developed coculture systems to define the interactions of adult human alveolar epithelial cells with lung fibroblasts. Alveolar type II cells cultured on floating collagen gels reduced the expression of type 1 collagen (COL1A1) and α-smooth muscle actin (ACTA2) in fibroblasts. They also reduced fibroblast expression of hepatocyte growth factor (HGF), fibroblast growth factor 7 (FGF7, KGF), and FGF10. When type II cells were cultured at an air-liquid interface to maintain high levels of surfactant protein expression, this inhibitory activity was lost. When type II cells were cultured on collagen-coated tissue culture wells to reduce surfactant protein expression further and increase the expression of some type I cell markers, the epithelial cells suppressed transforming growth factor-β (TGF-β)-stimulated ACTA2 and connective tissue growth factor (CTGF) expression in lung fibroblasts. Our results suggest that transitional alveolar type II cells and likely type I cells but not fully differentiated type II cells inhibit matrix and growth factor expression in fibroblasts. These cells express markers of both type II cells and type I cells. This is probably a normal homeostatic mechanism to inhibit the fibrotic response in the resolution phase of wound healing. Defining how transitional type II cells convert activated fibroblasts into a quiescent state and inhibit the effects of TGF-β may provide another approach to limiting the development of fibrosis after alveolar injury.

Role of Peripheral Benzodiazepine Receptors on Secretion of Surfactant in Guinea Pig Alveolar Type II Cells

1999 ◽  
Vol 19 (5) ◽  
pp. 461-471 ◽  
Author(s):  
Salil K. Das ◽  
Shyamali Mukherjee
Keyword(s):  
Pulmonary Surfactant ◽  
Benzodiazepine Receptors ◽  
Alveolar Epithelium ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Peripheral Tissues ◽  
Dipalmitoyl Phosphatidylcholine ◽  
Peripheral Benzodiazepine Receptors

Granular type II cells located in the alveolar epithelium synthesize and secrete pulmonary surfactant and have specialized ion transport system. Alveolar type II cells are stimulated to secrete pulmonary surfactant by a variety of agonists. One mechanism by which extracellular signals are perceived by cells is the mobilization of intracellular Ca2+. Peripheral benzodiazepine receptors (PBRs) are present in both peripheral tissues and central nervous system. We have previously reported the presence of high density PBRs in lung and alveolar type II cells. It is known that both PBRs and beta-adrenergic receptors (beta-ARs) play an important role in cellular Ca2+ transport. Furthermore, we have suggested earlier that PBRs are someway functionally associated with the beta-ARs. The objective of the present study was to determine whether PBRs play any role in the secretion of surfactant by alveolar type II cells. Alveolar type II cells were isolated from normal weanling guinea pigs by panning method and incubated with 3H-palmitic acid in minimum essential medium to synthesize labelled dipalmitoyl phosphatidylcholine (DPPC). After washing, the cells were treated at 37°C for one hour with 10 μM isoproterenol (IP) in the presence and absence of 10 μM Ro 5-4864, an agonist for PBRs. After one hour, the release of labelled DPPC in the medium was analyzed. The control cells released DPPC without any addition of a ligand. However, the treatment of cells with IP, Ro 5-4864 and IP + Ro 5-4864 caused 24, 52 and 171% increase in the secretion of DPPC, respectively. In another experiment, type II cells were loaded with Fura-2 dye and treated with either IP or epineprine or Ro 5-4864. Both isoproterenol and epinephrine caused a significant increase in the level of cytosolic free Ca2+. However, Ro 5-4864 caused not only a decrease in the level of cytosolic free Ca2+ but also counteracted the stimulatory effect of IP. This may suggest that while ligands for ARs stimulate Ca2+ release into cytosol, the ligand for PBRs stimulates efflux of Ca2+ in alveolar type cells. Thus, the increased secretion of surfactant by the ligand of PBRs in alveolar type II cells may be mediated through its effects on increased Ca2+ efflux.

scholarly journals Hepatocyte growth factor is elevated in chronic lung injury and inhibits surfactant metabolism

2000 ◽  
Vol 278 (2) ◽  
pp. L382-L392 ◽  
Author(s):  
Jeevalatha Vivekananda ◽  
Vibhudutta Awasthi ◽  
Shanjana Awasthi ◽  
Dolphin B. Smith ◽  
Richard J. King
Keyword(s):  
Growth Factor ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Pulmonary Surfactant ◽  
Distress Syndrome ◽  
Lung Fibroblasts ◽  
Type Ii Cells ◽  
Type Ii ◽  
Hepatocyte Growth

Adult respiratory distress syndrome may incorporate in its pathogenesis the hyperplastic proliferation of alveolar epithelial type II cells and derangement in synthesis of pulmonary surfactant. Previous studies have demonstrated that hepatocyte growth factor (HGF) in the presence of serum is a potential mitogen for adult type II cells (R. J. Panos, J. S. Rubin, S. A. Aaronson, and R. J. Mason. J. Clin. Invest. 92: 969–977, 1993) and that it is produced by fetal mesenchymal lung cells (J. S. Rubin, A. M.-L. Chan, D. P. Botarro, W. H. Burgess, W. G. Taylor, A. C. Cech, D. W. Hirschfield, J. Wong, T. Miki, P. W. Finch, and S. A. Aaronson. Proc. Natl. Acad. Sci. USA 88: 415–419, 1991). In these studies, we expand on this possible involvement of HGF in chronic lung injury by showing the following. First, normal adult lung fibroblasts transcribe only small amounts of HGF mRNA, but the steady-state levels of this message rise substantially in lung fibroblasts obtained from animals exposed to oxidative stress. Second, inflammatory cytokines produced early in the injury stimulate the transcription of HGF in isolated fibroblasts, providing a plausible mechanism for the increased amounts of HGF seen in vivo. Third, HGF is capable of significantly inhibiting the synthesis and secretion of the phosphatidylcholines of pulmonary surfactant. Fourth, HGF inhibits the rate-limiting enzyme in de novo phosphatidylcholine synthesis, CTP:choline-phosphate cytidylyltransferase (EC 2.7.7.15 ). Our data indicate that fibroblast-derived HGF could be partially responsible for the changes in surfactant dysfunction seen in adult respiratory distress syndrome, including the decreases seen in surfactant phosphatidylcholines.

Effect of secretagogues on cytoplasmic free calcium in alveolar type II epithelial cells

1987 ◽  
Vol 253 (5) ◽  
pp. C679-C686 ◽  
Author(s):  
K. Sano ◽  
D. R. Voelker ◽  
R. J. Mason
Keyword(s):  
Pulmonary Surfactant ◽  
Calcium Concentration ◽  
Free Calcium ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Surfactant Secretion ◽  
Free Calcium Concentration ◽  
Cytoplasmic Free Calcium

Pulmonary surfactant is synthesized and secreted by alveolar type II epithelial cells. Although intracellular calcium and other second messengers have been implicated in secretion by type II cells, this is the first report on measurement of cytoplasmic free calcium concentration ([Ca2+]i). Known secretagogues, 12-O-tetradecanoylphorbol-13-acetate (TPA) and terbutaline, were tested to see if they caused rapid increases in cytoplasmic calcium. Ionomycin, a calcium ionophore, was used to increase cytoplasmic free calcium concentration, to determine if a rapid increase in cytoplasmic free calcium would stimulate secretion, and to measure interactions with other secretagogues. Ionomycin increased both [Ca2+]i and pulmonary surfactant secretion from alveolar type II cells. A low concentration of ionomycin (100 nM) greatly enhanced secretion stimulated by terbutaline or by 8-bromo-cAMP but only had an additive effect on secretion stimulated by TPA. Terbutaline transiently increased [Ca2+]i by 24% over control basal condition, and the increase in [Ca2+]i produced by terbutaline occurred in the absence of extracellular calcium. TPA itself did not change [Ca2+]i. However, TPA completely inhibited the terbutaline-induced increase of [Ca2+]i but not the increase due to ionomycin. When alveolar type II cells were loaded with 2-(2-bis-[carboxymethyl]-amino-5-methyl-phenoxy)-methyl-6-methoxy-8-bis carboxymethylaminoquinoline (quin2) in calcium-free buffer, [Ca2+]i decreased from 143 +/- 10 to 31 +/- 8 nM. Lowering [Ca2+]i inhibited TPA- or terbutaline-induced secretion by 22 and 40%, respectively. Although the precise role of cytoplasmic free calcium on surfactant secretion cannot be established on the basis of current data, our results indicate that an increase in cytoplasmic free calcium produced by ionomycin stimulates secretion and that an increase in [Ca2+]i affects cAMP-induced secretion more than protein kinase C-mediated secretion in alveolar type II cells.

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