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Alveolar natural killer (NK) cells are functionally weak compared to their blood and interstitial counterparts. Having previously demonstrated that pulmonary surfactant suppresses lymphocyte responses to a variety of stimuli we sought in this study to determine if surfactant exerts a similar suppressive effect on cytotoxic function. Lipids were purified from the bronchoalveolar lavage (BAL) fluid from normal human volunteers. Human peripheral blood lymphocytes (n= 10 subjects) were cultured overnight in the presence or absence of purified BAL lipids (0.2 mg/ml), or pure preparations of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) (0.4 mg/ml). Standard NK and antibody-dependent cytotoxicity (ADCC) assays were performed using K562 and Chang target cells. The pooled BAL lipids significantly suppressed both NK (P < 0.01) and ADCC (P = 0.01) activity in a dose-dependent manner. Whereas pure PC did not exert a significant effect, PG significantly suppressed (P < 0.01) and PE significantly enhanced (P < 0.01) both cytotoxic functions. There was no change in the expression of leu 7 or 11 b antigens by lymphocytes after culture in BAL lipids. These results suggest that under normal circumstances pulmonary surfactant may suppress alveolar cytotoxic responses but that imbalances in the phospholipid profile might affect this immunoregulatory properly. [ABSTRACT FROM AUTHOR]

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 scrum-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 > PG > 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. [ABSTRACT FROM AUTHOR]