Cooperation between secretory phospholipase A2 and TNF-receptor signaling -: Implications for, the inflammatory response in atherogenesis
Cooperation between secretory phospholipase A2 and TNF-receptor signaling -: Implications for, the inflammatory response in atherogenesis
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DOI：
10.1161/01.res.0000038341.34243.64
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发表时间：
2002-10-18
影响因子：
20.1
通讯作者：
Nieto, ML
中科院分区：
文献类型：
--
作者：
Fuentes, L;Hernández, M;Nieto, ML
动脉粥样硬化是多种效应机制的结果，而不是单一功能分子的结果。在这方面，IIA型分泌型磷脂酶A（2）（sPLA（2））是一种急性期反应物，其在动脉粥样硬化的动脉壁中积累，对单核细胞产生多种作用，并且与动脉粥样硬化的发展有关。CD 40/CD 40配体对也是一个强的致动脉粥样硬化系统。sPLA（2）可增加THP-1单核细胞表面CD 40的表达，并增强CD 40连接对Fas和FasL表达的影响，表明sPLA（2）与TNF受体超家族不同成员之间存在正协同作用。用抗CD 40抗体激活CD 40/CD 40 L二联体产生少量花生四烯酸的释放，并且对环氧合酶-2的诱导没有任何显著影响，而趋化因子MCP-1的分泌和整合素Mac-1的α链CD 11b的表面展示被上调。CD 40的参与并不影响THP-1单核细胞的存活，但是用抗CD 40抗体和Jurkat细胞预处理的THP-1单核细胞的共孵育诱导了显示膜联蛋白-V结合的Jurkat细胞的数量的显著增加，以及核浓缩和碎片化，从而表明这种处理可能在敏感细胞类型中触发凋亡性死亡的促细胞分泌/旁分泌机制。该数据表明，对CD 40、TNF-α和sPLA的反应存在重叠途径（2），因此允许单核细胞中出现不同的反应模式。
Atherogenesis is the consequence of a variety of effector mechanisms rather than the result of a single functional molecule. In this connection, type IIA secretory phospholipase A(2) (sPLA(2)) is an acute-phase reactant, which accumulates in atherosclerotic arterial walls, elicits several effects on monocytes, and has been related to the development of atherosclerosis. CD40/CD40 ligand pair is also a strong proatherogenic system. sPLA(2) produced an increase of the surface expression of CD40 in THP-1 monocytes and enhanced the effect of CD40 ligation on the expression of both Fas and FasL, thus indicating the existence of a positive cooperation between sPLA2 and different elements of the TNF-receptor superfamily. Activation of the CD40/CD40L dyad with anti-CD40 antibody produced a small release of arachidonic acid and lacked any significant effect on the induction of cyclooxygenase-2, whereas the secretion of the chemokine MCP-1 and the surface display of CD11b, the alpha chain of the integrin Mac-1, were upregulated. Engagement of CD40 did not influence the survival of THP-1 monocytes, but coincubation of THP-1 monocytes pretreated with anti-CD40 antibody and Jurkat cells induced a significant increase of the number of Jurkat cells showing binding of annexin-V, and nuclear condensation and fragmentation, thus indicating that this treatment might trigger a juxtacrine/paracrine mechanism of apoptotic death in sensitive cell types. This data indicates the existence of overlapping routes for the response to CD40, TNF-alpha, and sPLA(2), thus allowing the development of distinct patterns of response in monocytic cells.