Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2
Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2
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DOI：
10.1172/jci25982
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发表时间：
2006-05-01
影响因子：
15.9
通讯作者：
Sjöholm, AG
中科院分区：
文献类型：
--
作者：
Selander, B;Mårtensson, U;Sjöholm, AG
已知C3的凝集素途径活化涉及甘露聚糖结合凝集素（MBL）或纤维胶凝蛋白的靶标识别以及通过MBL相关丝氨酸蛋白酶2（MASP-2）切割C4和C2产生经典途径C3转化酶。我们研究了C2缺陷的人血清和具有其他确定的补体缺陷的血清中的C3活化，以评估MBL可能通过其募集补体的其他机制。血清支持C3沉积的能力通过ELISA使用包被有来自鼠伤寒沙门氏菌、S. thompson和S.对应于血清群B、C和D（BO、CO和DO）的大肠杆菌。MBL与CO结合，但不与BO和DO结合，并且在不存在C2、C4或MASP-2的情况下有效地支持C3沉积。使用CO、固相甘露聚糖和E. coli LPS。MASP-1可能有所贡献，但在所用模型中不需要C3沉积。独立的MBL，特异性抗体CO支持C3沉积通过经典和替代途径。MBL依赖性C2旁路激活在各种遗传性和获得性补体缺乏状态中可能特别重要。
Lectin pathway activation of C3 is known to involve target recognition by mannan-binding lectin (MBL) or ficolins and generation of classical pathway C3 convertase via cleavage of C4 and C2 by MBL-associated serine protease 2 (MASP-2). We investigated C3 activation in C2-deficient human sera and in sera with other defined defects of complement to assess other mechanisms through which MBL might recruit complement. The capacity of serum to support C3 deposition was examined by ELISA using microtiter plates coated with 0 antigen-specific oligosaccharides derived from Salmonella typbimurium, S. thompson, and S. enteritidis corresponding to serogroups B, C, and D (BO, CO, and DO). MBL bound to CO, but not to BO and DO, and efficiently supported C3 deposition in the absence of C2, C4, or MASP-2. The existence of an MBL-dependent C2 bypass mechanism for alternative pathway-mediated C3 activation was clearly demonstrated using CO, solid-phase mannan, and E. coli LPS. MASP-1 might contribute, but was not required for C3 deposition in the model used. Independent of MBL, specific antibodies to CO supported C3 deposition through classical and alternative pathways. MBL-dependent C2 bypass activation could be particularly important in various inherited and acquired complement deficiency states.