title: Unaggregated serum IgA binds to neutrophil Fc alpha R at physiological concentrations and is endocytosed but cross-linking is necessary to elicit a respiratory burst.
abstract: My43 is a monoclonal antibody directed against Fc alpha Rs on monocytes that also recognizes neutrophil (PMN) Fc alpha Rs and is able to elicit a respiratory burst in purified cells. It appears to be directed against the immunoglobulin A (IgA) binding site of Fc alpha Rs or an epitope in close proximity, since IgA and My43 compete for binding to PMNs. My43 immunoblotted Fc alpha R that had been affinity purified from PMN membranes and immunoprecipitated a 50-70 kDa protein from radiolabeled PMN membranes, apparently identical to that purified on IgA-Sepharose. These results suggest the presence of a single class of Fc alpha R on PMNs. Binding of unaggregated monomeric or dimeric serum IgA to Fc alpha Rs on PMNs occurs at physiological concentrations, suggesting that in vivo Fc alpha Rs are saturated with ligand. This binding does not elicit a respiratory burst. Purified PMNs do not express surface IgA, since receptor-bound IgA is lost from the cell surface by endocytosis at room temperature although not at 4 degree C. Rapid endocytosis of receptor-bound IgA has been demonstrated by flow cytometry and confocal microscopy. Unoccupied receptor that is able to bind IgA or My43 is subsequently reexpressed. Cross-linking of surface-bound IgA using F(ab')2 anti-alpha chain antibodies triggers an oxidative burst. After internalization of the surface IgA the same F(ab')2 anti-alpha chain antibodies do not trigger the burst.
authors.affiliation: Department of Pathology, University of Dundee, Ninewells Hospital Medical School, Scotland.
authors.forename: W W
authors.initials: WW
authors.lastname: Stewart
authors.forename: R L
authors.initials: RL
authors.lastname: Mazengera
authors.forename: L
authors.initials: L
authors.lastname: Shen
authors.forename: M A
authors.initials: MA
authors.lastname: Kerr
mesh_terms: D004705:Endocytosis; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D008024:Ligands; D046911:Macromolecular Substances; D009504:Neutrophils / Q000502:physiology*; D011940:Receptor Aggregation; D011961:Receptors, Fc / Q000378:metabolism*; D016897:Respiratory Burst; D015398:Signal Transduction
chemical_list: C045281:IgA receptor; D007070:Immunoglobulin A; D008024:Ligands; D046911:Macromolecular Substances; D011961:Receptors, Fc