Identification of an IgA inhibitor of neutrophil chemotaxis and its membrane target for the metabolic burst.
Affinity-purified IgA from the serum of an 8-year-old boy with a 5-year history of recurrent facial nodules, intermittent neutropenia and elevated immunoglobulin levels, inhibited the chemotaxis of polymorphonuclear neutrophils (PMN) from both patient and normal adults. Preincubation of normal PMN with IgA from the patient's serum (0.5 mg/ml) inhibited chemotaxis to C5a and to the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) by 80%, while IgA or IgG from pooled human serum and IgG from the patient were without effect. Normal PMN chemotaxis was restored after IgA depletion of the patient's serum by affinity chromatography. The patient's IgA, but not IgA from pooled human serum, bound specifically to normal PMN by its antigen-binding sites and recognized a 62,000 MW membrane protein on normal neutrophils, which was distinct from the FMLP receptor, the C5a receptor, or the Fca receptor. Attachment of the patient's IgA to the 62,000 MW protein activated intracellular oxidative metabolism on a parity with phorbol myristate acetate (PMA) and resulted in a significant up-regulation of membrane receptors for FMLP. After the binding of patient (Pt) IgA, normal neutrophils were rendered significantly less responsive to subsequent stimulation with phorbol esters. These results characterize a novel mechanism of chemotactic inhibition by serum IgA and also identify a neutrophil membrane protein that is linked to intracellular oxidative metabolism.
Department of Pediatrics, University of Minnesota, Minneapolis.
J N
JN
Moy
R D
RD
Nelson
K L
KL
Richards
M K
MK
Hostetter
D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D002648:Child; D015936:Complement C5a / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007070:Immunoglobulin A / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010101:Oxygen Consumption
D007070:Immunoglobulin A; D008565:Membrane Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a