Enhancement of Complement Activation and Opsonophagocytosis by Complexes of Mannose-Binding Lectin with Mannose-Binding Lectin-Associated Serine Protease After Binding to Staphylococcus aureus1
Enhancement of Complement Activation and Opsonophagocytosis by Complexes of Mannose-Binding Lectin with Mannose-Binding Lectin-Associated Serine Protease After Binding to Staphylococcus aureus1
复制标题
甘露糖结合凝集素与甘露糖结合凝集素相关丝氨酸蛋白酶复合物与金黄色葡萄球菌结合后增强补体激活和调理吞噬作用1
作者：
O. Neth;D. Jack;Marina Johnson;N. Klein;M. Turner
人甘露糖结合凝集素（MBL）是先天免疫系统的血清蛋白，其作为与一组所谓的MBL相关丝氨酸蛋白酶（MASP-1、MASP-2和MASP-3）的复合物循环。MBL-MASP 2的复合物能够在凝集素与适当的微生物糖阵列结合后以Ab和Cl非依赖性方式激活补体系统。我们已经评估了凝集素途径相对于其他补体激活途径的附加效应以及对中性粒细胞吞噬作用的后续效应。在添加和不添加外源性MBL-MASP的情况下研究MBL缺陷个体的血清中的补体活化。流式细胞术用于测量C4、因子B、C3 B和iC 3 B在金黄色葡萄球菌上的沉积。当加入外源性MBL-MASP时，使用三种不同MBL缺陷个体的血清增加凝集素途径的第一裂解产物C4 b的沉积。因子B与C4相关沉积，但没有证据表明独立的旁路途径激活。还观察到C3 b沉积的类似增强，有证据表明C3 b加工成iC 3b的量升高。MBL介导的调理素C3片段的增加与嗜中性粒细胞对生物体摄取的显著增加相关。我们还观察到与补体活化无关的MBL-MASP的吞噬作用显著增加。我们得出结论，MBL-MASP作出了重大贡献，补体介导的宿主防御机制。
Human mannose-binding lectin (MBL) is a serum protein of the innate immune system that circulates as a complex with a group of so-called MBL-associated serine proteases (MASP-1, MASP-2, and MASP-3). Complexes of MBL-MASP2 are able to activate the complement system in an Ab and C1-independent fashion after binding of the lectin to appropriate microbial sugar arrays. We have evaluated the additive effect of the lectin pathway relative to other complement activation pathways and the subsequent effect on neutrophil phagocytosis. Complement activation in the sera of MBL-deficient individuals was studied with and without the addition of exogenous MBL-MASP. Flow cytometry was used to measure the deposition of C4, factor B, C3b, and iC3b on Staphylococcus aureus. Deposition of the first cleavage product of the lectin pathway, C4b, was increased using the sera of three different MBL-deficient individuals when exogenous MBL-MASP was added. Factor B was deposited in association with C4, but there was no evidence of independent alternative pathway activation. Similar enhancement of C3b deposition was also observed, with evidence of elevated amounts of C3b processed to iC3b. The increase in opsonic C3 fragments mediated by MBL was associated with a significant increase in the uptake of organisms by neutrophils. We also observed significant increases in phagocytosis with MBL-MASPs that were independent of complement activation. We conclude that MBL-MASP makes a major contribution to complement-mediated host defense mechanisms.
甘露糖结合蛋白 (MBP) 通过含有 C1q 受体 126,000 M(r) 成分的受体增强单核吞噬细胞功能。
影响因子：
32.4
作者：
Tenner,AJ;Robinson,SL;Ezekowitz,RA
通讯作者：
Ezekowitz,RA