Vascular regulation of type II cell exocytosis.
To determine whether lung capillary pressure regulates surfactant secretion, we viewed alveoli of the constantly inflated, isolated blood-perfused rat lung by fluorescence microscopy. By alveolar micropuncture we infused fura 2 and lamellar body (LB)-localizing dyes for fluorescence detection of, respectively, the alveolar cytosolic Ca(2+) concentration ([Ca(2+)](i)) and type II cell exocytosis. Increasing left atrial pressure (Pla) from 5 to 10 cmH(2)O increased septal capillary diameter by 26% and induced marked alveolar [Ca(2+)](i) oscillations that abated on relief of pressure elevation. The rate of loss of LB fluorescence that reflects the LB exocytosis rate increased fourfold after the pressure elevation and continued at the same rate even after pressure and [Ca(2+)](i) oscillations had returned to baseline. In alveoli pretreated with either 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, the intracellular Ca(2+) chelator, or heptanol, the gap junctional blocker, the pressure-induced exocytosis was completely inhibited. We conclude that capillary pressure and surfactant secretion are mechanically coupled. The secretion initiates in a Ca(2+)-dependent manner but is sustained by Ca(2+)-independent mechanisms.
Wang
P M
PM
Department of Medicine, College of Physicians and Surgeons; and St. Luke's-Roosevelt Hospital Center, Columbia University, New York, New York 10019, USA.
Fujita
E
E
Bhattacharya
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002196:Capillaries / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D005456:Fluorescent Dyes; D017629:Gap Junctions / Q000502:physiology; D019850:Heptanol / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D008297:Male; D008856:Microscopy, Fluorescence; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000166:cytology* / Q000502:physiology*; D011652:Pulmonary Circulation / Q000502:physiology*; D011663:Pulmonary Surfactants / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical
D002614:Chelating Agents; D005456:Fluorescent Dyes; D011663:Pulmonary Surfactants; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D019850:Heptanol; D002118:Calcium