Mitogen-activated protein kinase is activated during IgG-mediated phagocytosis, but is not required for target ingestion.
Arachidonic acid (AA) release is required for IgG-mediated phagocytosis in human monocytes. AA release is mediated by a calcium-independent phospholipase A2 (PPL) that is in turn regulated by protein kinase C (PKC). As mitogen-activated protein kinase (MAPK) activates cytosolic phospholipase A2, we examined the activation and involvement of MAPK in IgG-mediated phagocytosis. MAPK activity was assessed in immunoprecipitates; tyrosine phosphorylation was detected by immunoblotting. Ingestion of IgG-opsonized glass beads, or treatment with phorbol myristate acetate, increased enzymatic activity and tyrosine phosphorylation of p42 MAPK. This MAPK activation was attenuated by PKC inhibitors staurosporine or calphostin C. Treatment with PD98059, a p42/p44 MAPK kinase (MEK) inhibitor, decreased BIgG-stimulated p42 MAPK activity by > 90% with no significant effect on phagocytosis or pPL activity. These results suggest that p42 MAPK is activated in a PKC-dependent manner during IgG-dependent phagocytosis but is not required for target ingestion.
Karimi
K
K
Department of Physiology and Cell Biology, Albany Medical College, New York 12208, USA.
Lennartz
M R
MR
D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology; D009281:Naphthalenes / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D010740:Phospholipases / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology; D019311:Staurosporine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007074:Immunoglobulin G; D009281:Naphthalenes; D017452:Receptors, IgG; D019000:Phosphotyrosine; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D010740:Phospholipases; D019311:Staurosporine; C058819:calphostin C; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one