Cardiac myocytes activated by septic plasma promote neutrophil transendothelial migration - Role of platelet-activating factor and the chemokines LIX and KC
Cardiac myocytes activated by septic plasma promote neutrophil transendothelial migration - Role of platelet-activating factor and the chemokines LIX and KC
复制标题
DOI：
10.1161/01.res.0000124395.20249.ae
复制
发表时间：
2004-04-16
影响因子：
20.1
通讯作者：
Kvietys, PR
中科院分区：
文献类型：
--
作者：
Madorin, WS;Rui, T;Kvietys, PR
从腹膜炎（盲肠结扎穿孔; CLP）大鼠分离的心肌细胞促进PMN跨内皮迁移。在此，我们评估了（1）腹膜炎时心肌细胞激活的机制和（2）这些激活的心肌细胞促进PMN跨内皮迁移的方式。从经受CLP的小鼠获得的血浆（脓毒症血浆）激活分离的心肌细胞，如通过（1）核因子-ε B（NF-κ B）的核水平增加和（2）它们促进PMN迁移穿过内皮细胞单层的能力所证明的。用抗肿瘤坏死因子-α（TNF-α）的抗体预处理脓毒血症血浆，而不是白细胞介素-1 β（IL-1 β），减弱了脓毒血症血浆激活心肌细胞的能力。然而，从TNF-α缺陷小鼠获得的脓毒血症血浆仍然可以激活肌细胞; IL-1 β抗体减弱了这种作用。如果用蛋白酶体抑制剂（MG 132）预处理心肌细胞以防止NF-κ B活化，则心肌细胞诱导的PMN跨内皮迁移受到损害。活化的肌细胞释放血小板活化因子（PAF），肌细胞诱导的PMN迁移被PAF受体拮抗剂消除（WEB 2086）。这些肌细胞还释放CXC趋化因子LIX和KC; MG 132阻止了这一事件。抗LIX和KC的抗体可抑制肌细胞诱导的PMN迁移。然而，LIX和KC，而不是PAF，可以促进PMN迁移时，在激活的心肌细胞产生的浓度使用。这些观察结果表明，TNF-α和IL-1 β，部分负责脓毒血症血浆激活心肌细胞的能力。激活的心肌细胞促进PMN跨内皮迁移，这一作用归因于LIX和KC，可能还有PAF。
Cardiac myocytes isolated from rats with peritonitis (cecal ligation and perforation; CLP) promote PMN transendothelial migration. Herein, we assessed (1) the mechanisms involved in cardiac myocyte activation during peritonitis and ( 2) the means by which these activated myocytes promote PMN transendothelial migration. Plasma obtained from mice subjected to CLP (septic plasma) activated isolated cardiac myocytes as evidenced by (1) increased nuclear levels of nuclear factor-epsilonB (NF-kappaB) and (2) their ability to promote PMN migration across endothelial cell monolayers. Pretreatment of septic plasma with an antibody against tumor necrosis factor-alpha (TNF-alpha), but not interleukin-1beta (IL-1beta), blunted the ability of septic plasma to activate the myocytes. However, septic plasma obtained from TNF-alpha-deficient mice could still activate the myocytes; an effect attenuated by an antibody against IL-1beta. If the myocytes were pretreated with a proteasome inhibitor (MG 132) to prevent NF-kappaB activation, the myocyte-induced PMN transendothelial migration was compromised. The activated myocytes released platelet-activating factor (PAF), and myocyte-induced PMN migration was abrogated by a PAF receptor antagonist (WEB 2086). These myocytes also released the CXC chemokines LIX and KC; an event prevented by MG 132. Antibodies against LIX and KC abrogated the myocyte-induced PMN migration. However, LIX and KC, but not PAF, could promote PMN migration when used at concentrations produced by activated myocytes. These observations indicate that TNF-alpha and IL-1beta are, in part, responsible for the ability of septic plasma to activate cardiac myocytes. The activated myocytes promote PMN transendothelial migration, an effect attributable to LIX and KC, and possibly, PAF.