ANTIPHOSPHOLIPID ANTIBODIES - LOBSTERS OR RED HERRINGS

Membrane phospholipids, especially PS and PE, have been related to both spontaneous- and differentiation-related intercellular membrane fusion events, as well as spontaneous protein-free fusigenic reactions in model membrane systems. The same phospholipids are apparently related to the fusion competence of myoblast cells, being present at 35% and 25%, respectively, of the total PS and PE in the outer leaflet in fusion-incompetent cells and increasing to 65% and 45% within the outer leaflet of fusion-competent myoblasts. Cell fusion is also a necessary event during placental development; villous cytotrophoblast fuse to and contribute to the growing syncytium at the maternal-fetal interface. Platelets also undergo a localized and inducible fusion reaction as cytoplasmic granules fuse to the plasma membrane, resulting in a very localized mixing of inner and outer monolayer lipids, thereby exposing PS and PE to the extracellular fluid. Platelet activation also exposes PS separately from the fusion step. Thus, normal physiologic membrane fusion requirements for platelet activation and trophoblastic cell fusion are associated with PS exposure on the outer membrane surface. Because various localized transient nonbilaminar phases are associated with fusion events, the fusion-competent cytotrophoblast and the actively secreting platelets may also present antigenic conformations of PS. PS and PE may be more related to fusion competence because they can be perturbed to nonbilaminar forms, including an inverted micellar intermediate structure. Antigenic conformations of PS, therefore, may be accessible during, and potentially at sites of, normal membrane fusion.