Experimental and Clinical Research Center, A joint cooperation between the Charité and the Max-Delbrück Center for Molecular Medicine (MDC) and Department of Nephrology and Intensive Care Medicine, Charité University Health Services, Berlin, Germany.
Immunol Rev. 2016 Sep;273(1):232-48. doi: 10.1111/imr.12441.
Neutrophil serine proteases (NSPs) exercise tissue-degrading and microbial-killing effects. The spectrum of NSP-mediated functions grows continuously, not least because of methodological progress. Sensitive and specific FRET substrates were developed to study the proteolytic activity of each NSP member. Advanced biochemical methods are beginning to characterize common and specific NSP substrates. The resulting novel information indicates that NSPs contribute not only to genuine inflammatory neutrophil functions but also to autoimmunity, metabolic conditions, and cancer. Tight regulatory mechanisms control the proteolytic potential of NSPs. However, not all NSP functions depend on their enzymatic activity. Proteinase-3 (PR3) is somewhat unique among the NSPs for PR3 functions as an autoantigen. Patients with small-vessel vasculitis develop autoantibodies to PR3 that bind their target antigens on the neutrophil surface and trigger neutrophil activation. These activated cells subsequently contribute to vascular necrosis with life-threatening multiorgan failure. This article discusses various aspects of NSP biology and highlights translational aspects with strong clinical implications.
中性粒细胞丝氨酸蛋白酶 (NSPs) 具有组织降解和杀伤微生物的作用。NSP 介导的功能谱不断扩大，这不仅是因为方法学的进步。还开发了敏感和特异的 FRET 底物来研究每个 NSP 成员的蛋白水解活性。先进的生化方法开始表征常见和特异的 NSP 底物。由此产生的新信息表明，NSP 不仅有助于真正的炎症性中性粒细胞功能，而且有助于自身免疫、代谢状况和癌症。严格的调控机制控制 NSP 的蛋白水解潜力。然而，并非所有 NSP 功能都依赖于其酶活性。蛋白酶 3 (PR3) 在 NSP 中有些独特，因为 PR3 作为自身抗原的功能。小血管血管炎患者会产生针对 PR3 的自身抗体，这些抗体结合中性粒细胞表面的靶抗原并触发中性粒细胞激活。这些激活的细胞随后导致血管坏死和危及生命的多器官衰竭。本文讨论了 NSP 生物学的各个方面，并强调了具有强烈临床意义的转化方面。
