A monoclonal antibody specific for immunoglobulin A receptor triggers polymorphonuclear neutrophil superoxide release.
An immunoglobulin M (IgM) monoclonal antibody, My43, specific for IgA Fc receptor (Fc alpha R) on human monocytes, bound to human polymorphonuclear neutrophils (PMNs) and inhibited their ability to bind IgA but not IgG. It was observed that the PMN oxidative burst was induced by both polymeric IgA and aggregated IgG, whereas IgM was without effect. The IgG-mediated oxidative burst was inhibited by anti-Fc gamma RII Fab and anti-Fc gamma RIII F(ab')2 but not by My43. Conversely, the IgA-mediated oxidative burst was inhibited by My43 but not by anti-Fc gamma RII or anti-Fc gamma RIII. When anti-Fc receptor monoclonal antibodies (mAbs) were used directly as ligands, it was observed that both anti-Fc gamma RII Fab and anti-Fc gamma RII F(ab')2 promoted the oxidative burst when cross-linked. Moreover, My43, when cross-linked with F(ab')2 antimouse IgM, also triggered the oxidative burst, whereas an IgM anti-CD15 mAb, PM81, did not stimulate function. This demonstrates that IgA receptors on PMNs are function-triggering molecules and that an anti-IgA receptor mAb may be substituted as a ligand.
Shen
L
L
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03756.
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000502:physiology; D001667:Binding, Competitive; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D066298:In Vitro Techniques; D009504:Neutrophils / Q000502:physiology*; D011961:Receptors, Fc / Q000502:physiology; D017452:Receptors, IgG; D011971:Receptors, Immunologic / Q000502:physiology*; D016897:Respiratory Burst; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*; D010738:Type C Phospholipases / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; C045281:IgA receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D013481:Superoxides; D010738:Type C Phospholipases