Neutrophil lactoferrin release induced by IgA immune complexes can be mediated either by Fc alpha receptors or by complement receptors through different pathways.
Our previous results showed that neutrophil secondary granule release, indicated by release of lactoferrin, was a slow process when induced by IgA immune complexes (IC) formed in heat-inactivated serum, but became very fast if IgA IC were formed in normal human serum. This phenomenon did not apply to the IC of other Ab isotypes. In this paper, we demonstrate that the fast lactoferrin release is caused by complement, mainly due to the deposition of C3b and iC3b on IgA IC. Either CR1 or CR3 can mediate the response and both receptors have to be blocked to prevent it. Complement also influences FcalphaR-mediated lactoferrin release, in that this is enhanced by the anaphylatoxin peptides, C5a and C5a(desArg). Divalent cations are required for FcalphaR and CR3- but not for CR1-mediated lactoferrin release. Genistein, a protein tyrosine kinase inhibitor, totally inhibits FcalphaR-mediated response, but has little effect on CR1-mediated response. Therefore, it is clear that different pathways of intracellular signaling are utilized. In addition, stimulation through FcalphaR promotes the receptor up-regulation, which is abolished by the presence of EDTA or genistein.
Zhang
W
W
Molecular Immunopathology Unit, MRC Centre, Cambridge, United Kingdom.
Lachmann
P J
PJ
D000936:Antigen-Antibody Complex / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D007781:Lactoferrin / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010766:Phosphorylation; D011951:Receptors, Complement / Q000378:metabolism*; D017463:Receptors, Complement 3b / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation
D000936:Antigen-Antibody Complex; C045281:IgA receptor; D007070:Immunoglobulin A; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011961:Receptors, Fc; D014443:Tyrosine; D007781:Lactoferrin; D008274:Magnesium; D002118:Calcium