Induction of IL-4 by platelet-activating factor.
Platelet-activating factor (PAF) is a phospholipid inflammatory mediator which is synthesized by a variety of cells, including monocytes, endothelial cells, mast cells and neutrophils. PAF acts via a recently cloned PAF receptor, present on monocytes and endothelial cells, but not on non-activated lymphocytes. IL-4 is mainly produced by T lymphocytes, and belongs to the Th2 subset of T helper cells. IL-6 is mainly a monocyte/macrophage-derived cytokine with multiple proinflammatory effects. We here report that PAF induces IL-4 production, as determined by ELISPOT. Antibodies to MHC class II inhibited the IL-4 stimulatory effects of PAF. PAF also had the capacity to induce IgA production, as determined by ELISPOT, and IL-6 production in peripheral blood mononuclear cells (PBMC) as determined by ELISA. These PAF-mediated effects were completely inhibited by a specific PAF-receptor antagonist, WEB 2170. Taken together, our data indicate that PAF activates T lymphocytes to IL-4 production by an indirect, monocyte-dependent mechanism dependent on MHC class II. PAF also enhances antibody formation and IL-6 production from PBMC. These findings indicate that PAF activates immune-competent cells, which may be of importance in inflammatory diseases such as asthma, vasculitis and atherosclerosis.
Huang
Y H
YH
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Schäfer-Elinder
L
L
Owman
H
H
Lorentzen
J C
JC
Rönnelid
J
J
Frostegård
J
J
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001381:Azepines / Q000276:immunology; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles / Q000276:immunology
D000911:Antibodies, Monoclonal; D001381:Azepines; D000949:Histocompatibility Antigens Class II; D007070:Immunoglobulin A; D015850:Interleukin-6; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; D015847:Interleukin-4; C063964:bepafant