Immunosuppression by pulmonary surfactant: mechanisms of action.
Pulmonary surfactant has been shown by this group to suppress peripheral blood lymphocyte responses to mitogens and alloantigens in a dose dependent manner, though the mechanism of action of the suppressive effect is not clearly understood. To try to clarify this, attempts were made to reverse the effects of preincubation with surfactant, obtained by bronchoalveolar lavage from pigs, on lymphocytes and accessory monocytes obtained from the blood of normal volunteers, by washing and incubating the cells in medium alone for various periods up to 24 hours. Immunosuppression, measured as the reduction in thymidine incorporation in response to the mitogen phytohaemagglutinin, could not be reversed by these methods. The addition of indomethacin (up to 100 micrograms/ml for 72 hours) also had no effect, indicating that the immunosuppression was not related to synthesis of prostaglandins. Incubation with surfactant for as little as two hours before addition of mitogen suppressed in vitro lymphoproliferative responses by half, but surfactant added two hours after mitogen had no observed effect. Preincubation of purified lymphocytes in surfactant, before they were cultured with accessory monocytes and mitogen, caused significant suppression of response, but preincubation of purified monocytes had no suppressive effect. There was no change in the intensity of HLA-DR expression on monocytes. These results support the hypothesis that surfactant exerts its effects on the resting uncommitted lymphocyte rather than on antigen presenting monocytes.
Wilsher
M L
ML
Department of Cardiothoracic Surgery, National Heart and Lung Institute, London.
Parker
D J
DJ
Haslam
P L
PL
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007213:Indomethacin / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000276:immunology*; D013552:Swine; D013936:Thymidine / Q000378:metabolism
D010835:Phytohemagglutinins; D011663:Pulmonary Surfactants; D013936:Thymidine; D007213:Indomethacin