Antibodies against granule proteins activate neutrophils in vitro.
Polymorphonuclear leukocyte (PMN) respiratory burst was stimulated by heterologous antibodies against PMN granule proteins but not by control antibodies. Fluorescence-activated cell sorter (FACS) analysis of activated PMN demonstrated the presence of two primary granule proteins, proteinase 3 (PR-3) and cationic protein 57 (CAP-57) at the membrane surface. The presence of myeloperoxidase (MPO) at the cell surface of primed and unprimed PMN was confirmed by immunoelectron microscopy. Priming doses of recombinant tumor necrosis alpha (rTNF alpha) enhanced the rate of superoxide (O2-) production by these antibodies and increased the amount of surface protein accessible to these antibodies. Anti-neutrophil cytoplasmic autoantibodies (ANCA) with specificities for PMN granule proteins are present in patients with Wegener's granulomatosis, polyarteritis nodosa, and idiopathic and crescentic glomerulonephritis. The demonstration that antibodies against granule proteins activate PMN supports the hypothesis that the vasculitis seen in these diseases is due in part to PMN mediated oxidative injury following PMN stimulation by ANCA.
Charles
L A
LA
Department of Pathology, University of North Carolina School of Medicine, Chapel Hill 27599-7525.
Caldas
M L
ML
Falk
R J
RJ
Terrell
R S
RS
Jennette
J C
JC
D019268:Antibodies, Antineutrophil Cytoplasmic; D000937:Antigen-Antibody Reactions; D023181:Antimicrobial Cationic Peptides; D001323:Autoantibodies / Q000276:immunology*; D001798:Blood Proteins / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000502:physiology; D006801:Humans; D007700:Kinetics; D053146:Myeloblastin; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D016897:Respiratory Burst; D012697:Serine Endopeptidases / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D019268:Antibodies, Antineutrophil Cytoplasmic; D023181:Antimicrobial Cationic Peptides; D001323:Autoantibodies; D001798:Blood Proteins; D014409:Tumor Necrosis Factor-alpha; C053368:cationic antimicrobial protein 57, human; D013481:Superoxides; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin