The membrane attack complex of complement induces interleukin-8 and monocyte chemoattractant protein-1 secretion from human umbilical vein endothelial cells.
The membrane attack complex of complement induces interleukin-8 and monocyte chemoattractant protein-1 secretion from human umbilical vein endothelial cells.
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发表时间：
1996-09
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通讯作者：
Kenneth S. Kilgore;Craig M. Flory;B. Miller;Valary M. Evans;Jeffrey S. Warren
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作者：
Kenneth S. Kilgore;Craig M. Flory;B. Miller;Valary M. Evans;Jeffrey S. Warren
补体的膜攻击复合物（MAC）的细胞表面组装发生在各种病理生理学环境中。根据MAC形成的孔的密度和尺寸分布以及补体激活的膜调节剂的功能完整性，MAC可以引起直接细胞裂解或补体激活细胞。我们研究了亚溶解浓度的MAC诱导人脐静脉内皮细胞（HUVEC）分泌特异性α-和β-趋化因子的功能能力。由MAC引起的内皮细胞活化与补体依赖性炎症过程特别相关，包括缺血-再灌注损伤和急性肺损伤。亚溶解浓度的MAC对HUVECs的组装导致中性粒细胞和单核细胞趋化活性的顺序分泌。对携带MAC的HUVEC的条件培养基的分析表明，中性粒细胞趋化活性主要归因于白细胞介素（IL）-8，而随后检测到的单核细胞趋化活性（在8小时与4小时达到峰值）主要归因于MCP-1。MAC诱导的IL-8和MCP-1分泌的这种时间模式使用IL-8和MCP-1特异性酶联免疫吸附测定法证实。HUVECs的北方杂交分析显示MAC沉积伴随着IL-8和MCP-1 mRNA水平的增加。这些数据表明，HUVEC上的MAC的亚溶解浓度的组装可以诱导中性粒细胞和单核细胞趋化活性的顺序分泌，并且前者主要归因于IL-8，而后者主要归因于MCP-1。
Cell surface assembly of the membrane attack complex (MAC) of complement occurs in a variety of pathophysiological settings. Depending upon the density and size distribution of pores formed by the MAC and the functional integrity of membrane regulators of complement activation, the MAC can either cause direct cell lysis or transduce cell activation. We have examined the functional capacity of sublytic concentrations of MAC to induce the secretion of specific alpha- and beta-chemokines from human umbilical vein endothelial cells (HUVECs). Endothelial cell activation by the MAC has particular relevance to complement-dependent inflammatory processes including ischemia-reperfusion injury and acute lung injury. Assembly of sublytic concentrations of the MAC on HUVECs resulted in the sequential secretion of both neutrophil and monocyte chemotactic activities. Analysis of conditioned medium from MAC-bearing HUVECs revealed that the neutrophil chemotactic activity was largely attributable to interleukin (IL)-8, whereas the monocyte chemotactic activity, which was detected later (peak at 8 hours versus 4 hours), was largely attributable to MCP-1. This temporal pattern of MAC-induced secretion of IL-8 and MCP-1 was confirmed using IL-8- and MCP-1-specific enzyme-linked immunosorbent assays. Northern hybridization analysis of HUVECs revealed that MAC deposition was accompanied by an increase in IL-8 and MCP-1 mRNA levels. These data indicate that assembly of sublytic concentrations of the MAC on HUVECs can induce the sequential secretion of both neutrophil and monocyte chemotactic activities and that the former is largely attributable to IL-8 whereas the latter is largely attributable to MCP-1.