[Influence of monoclonal antibodies to human neutrophil antigens, HNA-1a/b and HNA-2a on phagocytosis].
Neutrophil antibodies frequently cause severe conditions such as transfusion-related acute lung injury, alloimmune/autoimmune neutropenia. As it was thought that surviving neutrophils would also be damaged from antibodies binding with the neutrophil membrane, we studied the functional influence of neutrophil antibodies on natural phagocytosis and immune phagocytosis by using neutrophil-specific monoclonal antibodies (MoAbs), TAG1: HNA-la on FgammaRIIIb, TAG2: HNA-1b on FgammaRIIIa/b, TAG3: FgammaRIIIa/b and TAG4: HNA-2a. In an inhibition assay of carbon particle phagocytosis as a representation of natural phagocytosis, neutrophils binding with TAG3 or TAG4 were inhibited from carbon particle-phagocytosis by 42.5% and 53.2% (% inhibition), respectively, but in an inhibition assay using TAG3 MoAb, HNA-2a strongly positive neutrophils were more weakly inhibited than HNA-2a weak-positive neutrophils, 39.2% and 54.0% (% inhibition), respectively. These results suggested that HNA-2a salvaged the inhibition process of natural phagocytosis by anti-FcgammaRIII antibodies. These results also suggested that natural phagocytosis would be inhibited when antibodies combined with every antigen on the cell membrane. In an inhibition assay of EA-rosette formation as a representation of immune phagocytosis, FcgammaRIII-specific MoAbs, TAG1, TAG2 and TAG3 inhibited EA-rosette formation, but HNA-2a-specific MoAb, TAG4, did not markedly inhibit EA-rosette formation. It was thought that neutrophil immune-phagocytosis would be inhibited by antibodies binding with FcgammaRIII, and that HNA-2a was not related to immune phagocytosis. Further investigation of the relationship between clinical symptoms and antibody specificity or antibody quantity is needed.
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology*; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D012128:Respiratory Distress Syndrome / Q000276:immunology; D012397:Rosette Formation
D000911:Antibodies, Monoclonal; C407242:CD177 protein, human; D058851:GPI-Linked Proteins; D007519:Isoantigens; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C067704:neutrophil-specific antigen NA1, human