Increased Fc alpha R expression and IgA-mediated function on neutrophils induced by chemoattractants.
The recent reports of receptors for IgA on blood and mucosal phagocytes suggest a more active role then previously thought for IgA in host defense. Using a mAb and flow cytometry we determined the expression of the Fc alpha R on resting and chemoattractant-stimulated blood neutrophils and compared them with mucosal neutrophils. Fc alpha R expression on blood neutrophils could be rapidly up-regulated in vitro, increasing three to fourfold within minutes of exposure to the chemoattractants FMLP (optimal at 10(-8) M) and zymosan activated serum (a source of C5a). The level of Fc alpha R expression found on neutrophils obtained from bronchoalveolar lavage of cystic fibrosis patients with chronic lung infection was almost identical to that found on blood neutrophils from the same patients maximally activated in vitro. The rise in Fc alpha R expression induced by 10(-8) M FMLP was rapid, with a plateau in 15 to 20 min, and was not inhibited by 10 mg/ml of cycloheximide or puromycin, suggesting that the mechanism of up-regulation involves translocation from intracellular storage pools. Ionomycin (2 mM) plus 1.2 mM CaCl2 also increased expression of Fc alpha R, and its effects were inhibited by EDTA. Trifluoperazine, an inhibitor of calmodulin and/or protein kinase C-dependent processes, blocked the increase in Fc alpha R expression induced by FMLP, but the effects of the chemoattractant were not blocked by EDTA, suggesting that intracellular stores of calcium are important in the physiologic regulation of Fc alpha R expression. Neutrophil superoxide production could be induced by aggregated IgA, and was increased if the neutrophils were pretreated with FMLP, correlating with the increase in Fc alpha R expression. The superoxide response to a suboptimal dose of aggregated IgG was unaffected by FMLP pretreatment, and antibodies to Fc gamma R failed to block the superoxide production induced by IgA. Thus, the increase in phagocyte surface expression of Fc alpha R induced by chemoattractants in vitro and on mucosal cells in vivo, and the concomitant increase in IgA-mediated function may greatly facilitate the defense of mucosal surfaces.
Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106.
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Hostoffer
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Krukovets
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Berger
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002118:Calcium / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D003550:Cystic Fibrosis / Q000503:physiopathology; D006801:Humans; D007070:Immunoglobulin A / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology; D007371:Interferon-gamma / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011961:Receptors, Fc; D011971:Receptors, Immunologic / Q000378:metabolism*; D011994:Recombinant Proteins; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation
C045281:IgA receptor; D007070:Immunoglobulin A; D011500:Protein Synthesis Inhibitors; D011961:Receptors, Fc; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007371:Interferon-gamma; D002118:Calcium