Autocrine/paracrine involvement of platelet-activating factor and transforming growth factor-beta in the induction of phosphatidylserine recognition by murine macrophages.
The specific recognition of phosphatidylserine (PS) by macrophages is believed to be one means by which effete and apoptotic cells expressing PS on their outer membrane leaflet are targeted for phagocytosis. The aim of this study was to better understand the autocrine/paracrine factors involved in beta-glucan induction of PS recognition by macrophages. We provide evidence that both platelet-activating factor (PAF) and TGF-beta are involved in beta-glucan induction of PS recognition. This is based on the observations that the PAF receptor antagonist WEB 2086 and Ab against TGF-beta each could partially inhibit beta-glucan-induced PS recognition when used alone and could completely inhibit induction when used in combination. PAF, like TGF-beta, was found to prime macrophages for PS recognition, which could then be triggered by costimulation with a nonspecific phagocytic stimulus, latex particles. We also provide evidence that the priming by PAF and that by TGF-beta can occur independently of each other. This is based on the observations that 1) PAF priming was not blocked by anti-TGF-beta Ab, nor was TGF-beta priming prevented by WEB 2086; and 2) PAF did not increase the steady state level of TGF-beta mRNA, and TGF-beta did not induce PAF synthesis in these cells.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D005936:Glucans / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D010718:Phosphatidylserines / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D005936:Glucans; D010718:Phosphatidylserines; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D016212:Transforming Growth Factor beta; C039351:platelet activating factor receptor