ACTIVATION OF GRANULOCYTES BY ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA) - A FC-GAMMA-RII-DEPENDENT PROCESS

ANCA have been demonstrated to induce the respiratory burst in primed neutrophils. In this study we have extended the investigations on neut rophil activation by ANCA directed against proteinase 3 (PR3), myelope roxidase (MPO) and lactoferrin (LF), and we have analysed the underlyi ng mechanisms. All three ANCA antigens were expressed on the cell surf ace of primed neutrophils. Superoxide production assayed by both cytoc hrome c reduction and oxidation of dihydrorhodamine 123, was induced b y heterologous polyclonal anti-MPO and anti-LF antibodies, and ANCA-po sitive plasma samples. Induction of superoxide production was dose-dep endent. F(ab')(2) fragments did not induce the respiratory burst. Bloc kade of Fc receptors by specific MoAbs showed that anti-Fc gamma RII a ntibodies were able to turn off the ANCA-induced respiratory burst, wh ereas anti-Fc gamma RIII antibodies did not. Plasma samples that induc ed the respiratory burst did not differ from samples that did not indu ce superoxide production with respect to ANCA titre, but had higher le vels of the IgG3 subclass of ANCA. Levels of the other subclasses of A NCA were comparable between those samples. We conclude that ANCA-induc ed activation of primed neutrophils is Fc gamma RII-dependent, and app ears to be facilitated by antibodies of the IgG3 subclass.