Mulder A H, Heeringa P, Brouwer E, Limburg P C, Kallenberg C G
Department of Clinical Immunology, University Hospital Groningen, The Netherlands.
Clin Exp Immunol. 1994 Nov;98(2):270-8. doi: 10.1111/j.1365-2249.1994.tb06137.x.
ANCA have been demonstrated to induce the respiratory burst in primed neutrophils. In this study we have extended the investigations on neutrophil activation by ANCA directed against proteinase 3 (PR3), myeloperoxidase (MPO) and lactoferrin (LF), and we have analysed the underlying mechanisms. All three ANCA antigens were expressed on the cell surface of primed neutrophils. Superoxide production assayed by both cytochrome c reduction and oxidation of dihydrorhodamine 123, was induced by heterologous polyclonal anti-MPO and anti-LF antibodies, and ANCA-positive plasma samples. Induction of superoxide production was dose-dependent. F(ab')2 fragments did not induce the respiratory burst. Blockade of Fc receptors by specific MoAbs showed that anti-Fc gamma RII antibodies were able to turn off the ANCA-induced respiratory burst, whereas anti-Fc gamma RIII antibodies did not. Plasma samples that induced the respiratory burst did not differ from samples that did not induce superoxide production with respect to ANCA titre, but had higher levels of the IgG3 subclass of ANCA. Levels of the other subclasses of ANCA were comparable between those samples. We conclude that ANCA-induced activation of primed neutrophils is Fc gamma RII-dependent, and appears to be facilitated by antibodies of the IgG3 subclass.
抗中性粒细胞胞浆抗体（ANCA）已被证明可诱导致敏中性粒细胞的呼吸爆发。在本研究中，我们扩展了针对蛋白酶3（PR3）、髓过氧化物酶（MPO）和乳铁蛋白（LF）的ANCA对中性粒细胞激活的研究，并分析了其潜在机制。所有三种ANCA抗原均在致敏中性粒细胞的细胞表面表达。通过细胞色素c还原和二氢罗丹明123氧化测定的超氧化物产生，由异源多克隆抗MPO和抗LF抗体以及ANCA阳性血浆样本诱导。超氧化物产生的诱导呈剂量依赖性。F(ab')2片段不诱导呼吸爆发。特异性单克隆抗体阻断Fc受体表明，抗FcγRII抗体能够关闭ANCA诱导的呼吸爆发，而抗FcγRIII抗体则不能。诱导呼吸爆发的血浆样本与未诱导超氧化物产生的样本在ANCA滴度方面没有差异，但具有较高水平的ANCA IgG3亚类。这些样本之间ANCA其他亚类的水平相当。我们得出结论，ANCA诱导的致敏中性粒细胞激活是FcγRII依赖性的，并且似乎由IgG3亚类抗体促进。
