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Induction of IL-4 by platelet-activating factor
Y H Huang1, L Schäfer-Elinder, H Owman
1Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
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.
Insights
Platelet-activating factor (PAF) stimulates T lymphocytes to produce IL-4 and enhances antibody and IL-6 production. These effects are mediated indirectly via monocytes and blocked by a PAF-receptor antagonist, suggesting roles in inflammatory diseases.
Area of Science:
- Immunology
- Inflammation research
Background:
- Platelet-activating factor (PAF) is a key inflammatory mediator produced by various immune cells.
- PAF signals through a specific receptor found on monocytes and endothelial cells.
- Interleukin-4 (IL-4) is a cytokine primarily produced by T helper 2 (Th2) lymphocytes, while IL-6 is a pro-inflammatory cytokine often derived from monocytes/macrophages.
Purpose of the Study:
- To investigate the role of Platelet-activating factor (PAF) in modulating immune cell responses, specifically IL-4, IL-6, and IgA production.
- To elucidate the cellular mechanisms underlying PAF-induced immune cell activation, including the involvement of monocytes and MHC class II.
Main Methods:
- Enzyme-linked immunospot (ELISPOT) assays were used to quantify IL-4 and IgA production.
- Enzyme-linked immunosorbent assay (ELISA) was employed to measure IL-6 production.
- Peripheral blood mononuclear cells (PBMC) were treated with PAF, and responses were assessed with and without MHC class II antibodies or a PAF-receptor antagonist (WEB 2170).
Main Results:
- PAF significantly induced IL-4 production from T lymphocytes, an effect dependent on monocytes and MHC class II.
- PAF also stimulated IgA production and IL-6 production in PBMC.
- All PAF-mediated effects were completely abrogated by the specific PAF-receptor antagonist, WEB 2170.
Conclusions:
- PAF activates T lymphocytes to produce IL-4 through an indirect, monocyte-dependent pathway involving MHC class II.
- PAF also enhances antibody formation and IL-6 production in PBMC, indicating its broad impact on immune-competent cells.
- These findings highlight the potential significance of PAF in the pathogenesis of inflammatory conditions like asthma, vasculitis, and atherosclerosis.