Role of transmethylation in the elicitation of an oxidative burst in macrophages |
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Authors: | E Pick D Mizel |
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Institution: | 1. Laboratory of Immunopharmacology, Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel;2. Laboratory of Microbiology and Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20205 U.S.A. |
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Abstract: | Elicited guinea pig peritoneal macrophages (MPs) respond by an oxidative burst (OB) to a variety of membrane stimulants. Evidence has recently accumulated, indicating that phospholipase A2 activation resulting in unsaturated fatty acid liberation is a prerequisite for the induction of an OB by some stimulants. We examined the effect of inhibiting adenosylmethionine-dependent phospholipid methylation on the capacity of MPs to produce superoxide (O2?) in response to membrane stimulation. We found that preincubation of MPs with the transmethylation inhibitor, 3-deazaadenosine (DZAdo), totally eliminated the induction of an OB by concanavalin A, wheat germ agglutinin, and N-formyl-l-methionyl-l-leucyl-l-phenylalanine and partially blocked O2? production in response to NaF, phospholipase C, digitonin, the ionophore A23187, and phorbol myristate acetate (PMA). The PMA-elicited OB was the most resistant to inhibition by DZAdo. Homocysteine thiolactone enhanced the blocking effect of DZAdo. These findings suggest that stimulated O2? production by guinea pig peritoneal MPs requires enzymatic methylation of an unknown substrate, most likely a membrane phospholipid. |
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Keywords: | To whom requests for reprints should be sent at Department of Human Microbiology Sackler School of Medicine Tel-Aviv University Tel-Aviv 69978 Israel |
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