Rooijakkers Suzan H M, Ruyken Maartje, Roos Anja, Daha Mohamed R, Presanis Julia S, Sim Robert B, van Wamel Willem J B, van Kessel Kok P M, van Strijp Jos A G
Eijkman Winkler Institute, University Medical Center Utrecht, G04.614, 3584 CX Utrecht, The Netherlands.
Nat Immunol. 2005 Sep;6(9):920-7. doi: 10.1038/ni1235. Epub 2005 Aug 7.
The complement system is pivotal in host defense but also contributes to tissue injury in several diseases. The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. The convertases catalyze C3b deposition on activator surfaces. Here we describe the identification of staphylococcal complement inhibitor, an excreted 9.8-kilodalton protein that blocks human complement by specific interaction with C4b2a and C3bBb. Staphylococcal complement inhibitor bound and stabilized C3 convertases, interfering with additional C3b deposition through the classical, lectin and alternative complement pathways. This led to a substantial decrease in phagocytosis and killing of Staphylococcus aureus by human neutrophils. As a highly active and small soluble protein that acts exclusively on surfaces, staphylococcal complement inhibitor may represent a promising anti-inflammatory molecule.
补体系统在宿主防御中起关键作用，但在多种疾病中也会导致组织损伤。C3转化酶（C4b2a和C3bBb）的组装是补体激活的前提条件。这些转化酶催化C3b沉积在激活剂表面。在此，我们描述了葡萄球菌补体抑制剂的鉴定，这是一种分泌型9.8千道尔顿蛋白，通过与C4b2a和C3bBb特异性相互作用来阻断人类补体。葡萄球菌补体抑制剂结合并稳定C3转化酶，通过经典、凝集素和替代补体途径干扰额外的C3b沉积。这导致人类中性粒细胞对金黄色葡萄球菌的吞噬和杀伤作用大幅降低。作为一种仅作用于表面的高活性小可溶性蛋白，葡萄球菌补体抑制剂可能是一种有前景的抗炎分子。
