Monoclonal antibodies to CD45 modify LPS-induced arachidonic acid metabolism in macrophages.
Signaling by lipopolysaccharide (LPS) through CD14 involves the activation of protein tyrosine kinases of the src family and leads to cytokine production and activation of arachidonic acid metabolism in macrophages. CD45 protein tyrosine phosphatase (PTPase) might play a role in modulating the response through this pathway. Although a critical role in regulation of T-cell signaling for CD45 has been demonstrated, little is known about its role in macrophages. Monoclonal antibodies to CD45 and F(ab')(2) fragments of the monoclonal antibody enhanced the response of differentiated THP-1 monocytic cells to LPS for the release of radiolabeled arachidonic acid metabolites, prostaglandin E(2), and tumor necrosis factor alpha. The enhancing effect of anti-CD45 mAbs was shown to occur primarily through CD14-dependent signaling by performing the experiments under conditions favoring that pathway. Further, LPS may be able to alter the enzymatic activity of CD45, as shown by Western blots of CD45 immunoprecipitates in which LPS caused a transient change in the phosphorylation state of CD45. We conclude that CD45 appears to play a role in LPS-induced responses through the CD14 pathway, possibly through its PTPase activity.
Pfau
J C
JC
Division of Biological Sciences, Stella Duncan Memorial Research Institute, University of Montana, Missoula, MT 59812, USA. jpfau@selway.umt.edu
Walker
E
E
Card
G L
GL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000276:immunology* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D011961:Receptors, Fc / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D017493:Leukocyte Common Antigens; D015232:Dinoprostone