Nonsteroidal antiinflammatory agents inhibit upregulation of CD11b, CD11c, and CD35 in neutrophils stimulated by formyl-methionine-leucine-phenylalanine.
Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit PMN aggregation, chemotaxis, degranulation, and superoxide anion production stimulated by synthetic formyl peptides. Many of these functions are dependent upon receptors for the complement components C3b and iC3b (CD35 and CD11b, respectively), or the adherence molecules CD11b and CD11c. Using flow cytometry and specific monoclonal antibodies, we studied the effects of the NSAID piroxicam and indomethacin on the upregulation of these cell surface proteins on PMNs stimulated with FMLP, C5a, or ionomycin. Incubation of PMNs at 37 degrees C increased the expression of all three of these surface proteins. A further increase was induced by stimulation with FMLP, C5a, or ionomycin. Both piroxicam and indomethacin inhibited FMLP-induced upregulation of CD11b, CD11c, and CD35, but neither drug affected the upregulation of these surface molecules induced by C5a or ionomycin. Furthermore, piroxicam had no effect on 37 degrees C-induced upregulation of any of the surface proteins, while indomethacin showed no effect on 37 degrees C-induced CD11b upregulation but suppressed CD11c and CD35 upregulation. Inhibition of surface protein upregulation by FMLP was not due to inhibition of FMLP binding to PMNs. We conclude that piroxicam and indomethacin inhibit FMLP receptor-mediated upregulation of CD11b, CD11c, and CD35 in PMNs, but have no effect on the upregulation of these molecules by ionomycin or C5a. These data suggest that piroxicam and indomethacin interfere with postreceptor signaling events specific to PMN stimulation by FMLP.
Crowell
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Department of Medicine, University of New Mexico School of Medicine, Albuquerque 87131.
Van Epps
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D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism; D015936:Complement C5a / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016167:Integrin alphaXbeta2; D015759:Ionomycin / Q000494:pharmacology; D016177:Macrophage-1 Antigen; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010894:Piroxicam / Q000494:pharmacology; D011951:Receptors, Complement / Q000378:metabolism; D017463:Receptors, Complement 3b; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism; D013268:Stimulation, Chemical; D015854:Up-Regulation / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D016167:Integrin alphaXbeta2; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D016028:Receptors, Leukocyte-Adhesion; D010894:Piroxicam; D015759:Ionomycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D007213:Indomethacin