Lung annexin II promotes fusion of isolated lamellar bodies with liposomes.
The role of annexin II in the secretion of lung surfactant was investigated using isolated lamellar bodies and/or liposomes as the model system for aggregation and fusion. We first compared membrane aggregation mediated by two forms of annexin II, annexin II monomer (Anx IIm) and annexin II tetramer (Anx IIt). Anx IIt required 20-fold less Ca2+ to mediate phosphatidylserine (PS) liposome aggregation compared to Anx IIm. Aggregation of lamellar bodies mediated by Anx IIt was 4-fold greater than that by Anx IIm at 1 mM Ca2+. These results suggest that Anx IIt may be the more active form in vivo. Fusion of lamellar bodies with PS liposomes was promoted by Anx IIt in a dose-dependent manner, with maximal fusion occurring at 10-15 micrograms/ml of Anx IIt. Fusion was dependent on Ca2+ and the phospholipid composition of liposomes. While the fusion of lamellar bodies with PS liposomes required 100 microM Ca2+, the fusion with PS/phosphatidylethanolamine (PE) (1:3) liposomes required only 10 microM Ca2+. Anx IIt-mediated lamellar body-liposome fusion was enhanced by arachidonic acid, a lung surfactant secretagogue and inhibited by 4.4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of lung surfactant secretion. The data suggest that Anx IIt may play a role in the fusion of lamellar bodies with plasma membranes during lung surfactant secretion.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D017306:Annexin A2 / Q000737:chemistry / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D008081:Liposomes; D008168:Lung / Q000737:chemistry*; D046911:Macromolecular Substances; D008297:Male; D008561:Membrane Fusion / Q000187:drug effects*; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D017306:Annexin A2; D008081:Liposomes; D046911:Macromolecular Substances; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D016718:Arachidonic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium