LUNG ANNEXIN-II PROMOTES FUSION OF ISOLATED LAMELLAR BODIES WITH LIPOSOMES

The role of annexin II in the secretion of lung surfactant was investi gated using isolated lamellar bodies and/or liposomes as the model sys tem 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 I Im. Aggregation of lamellar bodies mediated by Anx IIt was 4-fold grea ter 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 wit h PS liposomes was promoted by Anx IIt in a dose-dependent manner, wit h maximal fusion occurring at 10-15 mu g/ml of Anx IIt. Fusion was dep endent on Ca2+ and the phospholipid composition of liposomes. While th e fusion of lamellar bodies with PS liposomes required 100 mu M Ca2+, the fusion with PS/phosphatidylethanolamine (PE) (1:3) liposomes requi red only 10 mu M Ca2+. Anx IIt-mediated lamellar body-liposome fusion was enhanced by arachidonic acid, a lung surfactant secretagogue and i nhibited 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 membr anes during lung surfactant secretion.