ANTIBODIES AGAINST GRANULE PROTEINS ACTIVATE NEUTROPHILS INVITRO

ANTIBODIES AGAINST GRANULE PROTEINS ACTIVATE NEUTROPHILS INVITRO
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DOI:
10.1002/jlb.50.6.539
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发表时间:
1991-12-01
影响因子:
5.5
通讯作者:
JENNETTE, JC
JENNETTE, JC
中科院分区:
医学3区
文献类型:
--
作者:
CHARLES, LA;CALDAS, MLR;JENNETTE, JC

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多形核白细胞(PMN)呼吸爆发可被抗中性粒细胞颗粒蛋白的异源抗体刺激,但不能被对照抗体刺激。荧光激活细胞分类器(FACS)对活化的PMN的分析表明,膜表面存在两种主要的颗粒蛋白,即蛋白酶3(PR-3)和阳离子蛋白57(CAP-57)。免疫电子显微镜证实髓过氧化物酶(MPO)存在于PMN细胞表面。重组肿瘤坏死因子α(rTNF-α)的启动剂量增加了这些抗体产生超氧化物(O2-)的速率,并增加了这些抗体可获得的表面蛋白的数量。具有PMN颗粒蛋白特异性的抗中性粒细胞胞浆抗体(ANCA)存在于韦格纳肉芽肿、结节性多动脉炎、特发性和新月体肾炎患者中。抗颗粒蛋白抗体激活PMN的实验结果支持这样一种假设,即这些疾病中出现的血管炎部分是由于ANCA刺激PMN后PMN介导的氧化损伤。
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.