Induction of IL-4 by platelet-activating factor |
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Authors: | Y. H. HUANG,L. SCH FER-ELINDER,H. OWMAN,J. C. LORENTZEN,J. R
NNELID,J. FROSTEG RD |
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Affiliation: | Department of Medicine, Division of Rheumatology, Karolinska Hospital, Stockholm, Sweden;*Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden |
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Abstract: | 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. |
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Keywords: | platelet-activating factor T lymphocyte IL-4 antibodies IL-6 |
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