Immunoregulatory functions of paf-acether. I. Effect of paf-acether on CD4+ cell proliferation.
Paf-acether or platelet-activating factor (1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a phospholipid mediator of inflammation initially described as a potent platelet-aggregating compound. It is newly formed by a variety of cells including monocytes and is now recognized as a major mediator of cell-cell interactions. The present studies were undertaken to determine whether paf-acether could modulate T cell function. We found that addition of paf-acether to CD4+ cells cultured with phytohemagglutinin markedly inhibited the proliferative response in a dose-dependent manner. Maximal inhibition occurred when paf-acether was present during the first 24 hr of cell culture and the presence of paf-acether did not alter the kinetics of CD4+ cell proliferation. Importantly, the mechanism by which paf-acether inhibited the proliferative response was not related to inhibition of interleukin 2 (IL-2) secretion since the amount of IL-2 in cultures was not altered and addition of exogenous IL-2 failed to restore the CD4+ cell proliferative response. Further, as judged by indirect immunofluorescence, paf-acether did not inhibit IL-2 receptor expression. Taken together, these data indicate that paf-acether interferes with some processes leading to CD4+ cell proliferation. This new role for the chemically defined monokine paf-acether emphasizes the potential role of inflammatory lipid mediators in the regulation of T cell response.
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D012636:Secretory Rate / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013997:Time Factors
D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D010835:Phytohemagglutinins; D010972:Platelet Activating Factor; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2