WEGENER GRANULOMATOSIS AUTOANTIBODIES IDENTIFY A NOVEL DIISOPROPYLFLUOROPHOSPHATE BINDING-PROTEIN IN THE LYSOSOMES OF NORMAL HUMAN-NEUTROPHILS
WEGENER GRANULOMATOSIS AUTOANTIBODIES IDENTIFY A NOVEL DIISOPROPYLFLUOROPHOSPHATE BINDING-PROTEIN IN THE LYSOSOMES OF NORMAL HUMAN-NEUTROPHILS
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DOI：
10.1172/jci114335
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发表时间：
1989-11-01
影响因子：
15.9
通讯作者：
VONDEMBORNE, AEGK
中科院分区：
文献类型：
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作者：
GOLDSCHMEDING, R;VANDERSCHOOT, CE;VONDEMBORNE, AEGK
与韦格纳S肉芽肿相关的抗中性粒细胞胞浆自身抗体被发现是针对盐溶糖蛋白三联体的，该三联体在十二烷基硫酸钠凝胶上以29000、30500和32000条不同的条带迁移，并存在于亲天蓝颗粒中。该抗原可被所有胞浆染色(C)-ANCA阳性的韦格纳S病患者血清特异性识别。C-ANCA抗原与[~3H]二丙基氟磷酸结合，表明它是一种丝氨酸蛋白酶，但与弹性蛋白酶和组织蛋白酶G明显不同。FMLP刺激细胞松弛素B处理的中性粒细胞释放C-ANCA抗原。提示C-ANCA在体内可能与C-ANCA抗原在炎症刺激下释放后发生相互作用。我们进一步证明，在一些核周染色(P-ANCA)患者的血清中可以检测到抗其他髓系溶酶体酶的自身抗体，如抗髓过氧化物酶和抗弹性蛋白酶。因此，C-ANCA和P-ANCA代表了一类新的针对髓系溶酶体酶的自身抗体。最初描述的Wegener特异性C-ANCA显示出对29,000个丝氨酸蛋白酶的明显一致的特异性。相反，P-ANCA可能识别髓过氧化物酶以及弹性蛋白酶和/或其他抗原。
Anti-neutrophil cytoplasmic autoantibodies (ANCA) specifically associated with Wegener''s granulomatosis were found to be directed against a saline-soluble glycoprotein triplet that migrates on SDS gels as distinct bands of Mr 29,000, 30,500, and 32,000 and is present in the azurophilic granules. This antigen was specifically recognized by all cytoplasmic-staining (C)-ANCA-positive sera from patients with Wegener''s disease. C-ANCA antigen bound [3H]disopropylfluorophosphate, which indicates that it is a serine protease, but it could clearly be distinguished from the serine proteases elastase and cathepsin G. Stimulation of cytochalasin B-treated neutrophils with FMLP induced release of C-ANCA antigen. This indicates that in vivo C-ANCA might interact with the C-ANCA antigen after its release upon inflammatory stimulation. We further demonstrate that in some perinuclear staining (P-ANCA) patients'' sera autoantibodies against other myeloid lysosomal enzymes can be detected, such as antimyeloperoxidase and antielastase. C-ANCA and P-ANCA thus represent a novel class of autoantibodies directed against myeloid lysosomal enzymes. The originally described Wegener-specific C-ANCA show an apparently uniform specificity for the 29,000 serine protease. In contrast, P-ANCA may recognize myeloperoxidase as well as elastase and/or other antigens.