The aim of this study was to seek in vitro evidence to support our hypothesis that the immunosuppressive properties of pulmonary surfactant might be influenced by variations in phospholipid composition. Dose response studies conducted in serum-free medium, have demonstrated that pure phospholipids of the major types found in pulmonary surfactant, namely phosphatidylcholine (PC), phosphatidylglycerol (PG) and phosphatidylinositol (PI) exhibit significant dose dependent suppression of lymphocyte response to phytohaemagglutinin (PHA) (PC greater than PG greater than PI). By contrast, phosphatidylethanolamine (PE), sphingomyelin (SM), and the neutral lipid cholesterol (CH) augment the lymphoproliferative response in serum-free medium. The degree of suppression obtained using mixtures of various ratios of PC, PG and PI depended on the proportion of the most suppressive phospholipids (PC and PG). Similarly, increasing the proportion of PC in mixtures containing variable proportions of PE or CH resulted in increasing suppression of lymphoproliferation. Comparisons of the lipid fractions purified from pulmonary surfactant of three species (human, pig and rabbit) showed that the levels of suppression they induced reflected their relative content of phospholipids with the greatest immunosuppressive properties. We conclude that variations in phospholipid composition may affect the immunoregulatory properties of pulmonary surfactant
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