Therapeutic intervention with complement and β-glucan in cancer
Therapeutic intervention with complement and β-glucan in cancer
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DOI：
10.1016/s0162-3109(99)00013-2
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发表时间：
1999-05-01
期刊：
影响因子：
--
通讯作者：
Vetvicková, J
中科院分区：
文献类型：
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作者：
Ross, GD;Vetvicka, V;Vetvicková, J
补体（C）有两个主要的效应系统可用于宿主防御。由组分C5-C9产生的膜攻击复合物（MAC）可形成穿透膜的损伤，其通过引起细胞质组分的快速损失而导致细胞死亡。MAC仅对具有外部磷脂膜的病原体有效，并且不能杀死革兰氏阳性细菌或其膜被细胞壁保护的酵母。C最重要的效应机制是微生物病原体与血清蛋白C3的调理作用，导致它们与吞噬细胞的C3受体的高亲和力附着。激活补体的病原体首先用C3的C3 b片段包被，C3的C3 b片段被血清因子I快速蛋白水解成iC 3b片段。这些iC 3b片段用于促进“经iC 3b调理的”病原体与吞噬细胞和自然杀伤（NK）细胞的iC 3b受体（CR 3、CD 11b/CD 18）的高亲合力附着，刺激吞噬作用和/或细胞毒性脱粒。宿主细胞，包括肿瘤细胞，已经被赋予了针对MAC和CR 3的细胞毒性活化的自我保护的天然机制。本综述讨论了一种新型的癌症免疫疗法，该疗法使用可溶性酵母β-葡聚糖来克服iC 3b调理的肿瘤细胞对吞噬细胞和NK细胞CR 3的细胞毒性激活的正常抵抗力，从而使C系统的这种重要效应机制以与其通常对细菌和酵母发挥作用相同的方式对肿瘤细胞发挥作用。此外，经iC 3b调理的肿瘤对β-葡聚糖引发的NK细胞CR 3的细胞毒性活化显示伴随细胞因子TNF α、IFN α、IFN γ和IL-6的肿瘤局部分泌。(C)1999 Elsevier Science B. V.保留所有权利。
Complement (C) has two major effector systems available for host defense. The membrane attack complex (MAC) generated from components C5-C9 can form membrane-penetrating lesions that lead to cell death by causing a rapid loss of cytoplasmic components. The MAC is only effective against pathogens with outer phospholipid membranes, and cannot kill Gram-positive bacteria or yeast whose membranes are protected by cell walls. The most important effector mechanism of C is the opsonization of microbial pathogens with the serum protein C3 that leads to their high avidity attachment to the C3-receptors of phagocytic cells. Pathogens that activate complement are first coated with the C3b fragment of C3, which is rapidly proteolyzed into the iC3b fragment by serum factor I. These iC3b fragments serve to promote the high avidity attachment of the 'iC3b-opsonized' pathogens to the iC3b-receptors (CR3, CD11b/CD18) of phagocytic cells and natural killer (NK) cells, stimulating phagocytosis and/or cytotoxic degranulation. Host cells, including neoplastic tumor cells, have been endowed with natural mechanisms for self-protection against both the MAC and the cytotoxic activation of CR3. This review discusses a novel type of immunotherapy for cancer that uses soluble yeast beta-glucan to override the normal resistance of iC3b-opsonized tumor cells to the cytotoxic activation of phagocyte and NK cell CR3, allowing this important effector mechanism of the C system to function against tumor cells in the same way that it normally functions against bacteria and yeast. Moreover, the cytotoxic activation of beta-glucan-primed NK cell CR3 by iC3b-opsonized tumors is shown to be accompanied by a tumor-localized secretion of the cytokines TNF alpha, IFN alpha, IFN gamma, and IL-6. (C) 1999 Elsevier Science B.V. All rights reserved.