Surfactant-associated protein inhibits phospholipid secretion from type II cells.
Secretion of [3H]phosphatidylcholine ([3H]PC) from isolated rat pulmonary type II epithelial cells was inhibited by the surfactant-associated protein of Mr = 35,000 (SAP-35) purified from canine lung surfactant. SAP-35 inhibited [3H]PC secretion in a dose-dependent manner and significantly inhibited basal, phorbol ester, beta-adrenergic, and P2-purinergic agonist-induced [3H]PC secretion. SAP-35 significantly inhibited [3H]PC secretion from 1 to 3 h after treatment. The IC50 for inhibition of [3H]PC secretion by canine SAP-35 was 1-5 X 10(-6) g/ml and was similar for inhibition of both basal and secretagogue-stimulated release. Heat denaturation of SAP-35, addition of monoclonal anti-SAP-35 antibody, reduction and alkylation of SAP-35, or association of SAP-35 with phospholipid vesicles reversed the inhibitory effect on secretagogue-induced secretion. Inhibitory effects of SAP-35 were observed 3 h after cells were washed with buffer that did not contain SAP-35. Although SAP-35 enhanced reassociation of surfactant phospholipid with isolated type II cells, its inhibitory effect on secretion of [3H]PC did not result from stimulation of reuptake of secreted [3H]PC by type II cells. The inhibition of phospholipid secretion by SAP-35 was also not due to inhibition of PC or disaturated PC synthesis by SAP-35. SAP-35, the major phospholipid-associated protein in pulmonary surfactant, is a potent inhibitor of surfactant secretion from type II cells in vitro and may play an important role in homeostasis of surfactant in the alveolar space.
Rice
W R
WR
Pediatrics/Neonatology Division, University of Cincinnati College of Medicine, Ohio 45267.
Ross
G F
GF
Singleton
F M
FM
Dingle
S
S
Whitsett
J A
JA
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002477:Cells / Q000145:classification; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010713:Phosphatidylcholines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011510:Proteolipids / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000031:analogs & derivatives*; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D051381:Rats
D010713:Phosphatidylcholines; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C445842:SFTPA1 protein, human; D000255:Adenosine Triphosphate