Relationship of ability of phospholipids to stimulate growth and bind to macrophages

Among the phospholipids normally present in mammalian cell membranes, the negatively charged phospholipids, phosphatidylserine (PS), phosphatidylglycerol, and cardiolipin, and the neutral phospholipid phosphatidylethanolamine--but not phosphatidylcholine (PC) or sphingomyelin--were found to induce growth of peripheral macrophages. By use of liposomes prepared from PS, which stimulated growth, and PC, which did not, the relation between growth-stimulating activity and binding of the phospholipids to macrophages was studied. The growth-stimulating activity of PS/PC liposomes decreased with increase in their relative content of PC. The amount of PS bound to macrophages also decreased with increase in the proportion of PC in PS/PC liposomes. These decreases in growth-stimulating and binding activities were both partly recovered by additional incorporation into the PS/PC liposomes of cholesterol, which is also a cell membrane component. Phospholipids that stimulated macrophage growth showed high binding ability to macrophages, whereas those that did not stimulate growth scarcely bound to macrophages. Thus the macrophage growth-stimulating activities of phospholipids correlated well with their ability to bind to macrophages. These liposome models should be useful in elucidating the early mechanism of induction of macrophage growth by lipid materials such as cell debris and lipoproteins.