Differential ability of exogenous chemotactic agents to disrupt transendothelial migration of flowing neutrophils
Differential ability of exogenous chemotactic agents to disrupt transendothelial migration of flowing neutrophils
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DOI：
10.4049/jimmunol.164.11.5961
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发表时间：
2000-06-01
影响因子：
4.4
通讯作者：
Nash, GB
中科院分区：
文献类型：
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作者：
Luu, NT;Rainger, GE;Nash, GB
中性粒细胞通过有序的粘附相互作用和激活信号在内皮细胞中迁移。为了研究这一序列被破坏的后果，我们研究了中性粒细胞灌注在经tnf - α处理4小时的HUVEC上的粘附和迁移，并评估了外源添加的趋化剂引起的变化。当用2 U/ml TNF处理HUVEC时，流动的中性粒细胞粘附，大多数滚动，相对较少通过单层迁移。如果将fMLP， IL-8，酶活性血浆（活化补体因子C5a的来源），上皮细胞源性中性粒细胞激活肽（ena78）或生长调节癌基因gro - α灌注到这些中性粒细胞上，它们停止滚动并迅速迁移单层，但不穿透单层。当100 U/ml TNF处理HUVEC时，大多数粘附的中性粒细胞转移。如果中性粒细胞在HUVEC上灌注前用fMLP、IL-8、C5a、ENA-78或GRO-alpha处理，可消除迁移，但不消除粘附。然而，当使用血小板活化因子激活中性粒细胞时，通过100 U/ml TNF处理的HUVEC的迁移并未受到损害，通过2 U/ml TNF处理的HUVEC的迁移实际上增加了。迁移需要在中性粒细胞上连接CXC趋化因子受体-2，并且该受体的差异脱敏（例如，通过fMLP而不是血小板活化因子）可以解释迁移中断的模式。因此，转运可能需要以正确的顺序呈现正确的激活剂，而不适当的激活（例如，通过全身激活剂）可能导致中性粒细胞在血管腔内的病理性积累。
Neutrophils migrate through endothelium using an ordered sequence of adhesive interactions and activating signals. To investigate the consequences of disruption of this sequence, we characterized adhesion and migration of neutrophils perfused over HUVEC that had been treated with TNF-alpha for 4 h and evaluated changes caused by exogenously added chemotactic agents. When HUVEC were treated with 2 U/ml TNF, flowing neutrophils adhered, with the majority rolling and relatively few migrating through the monolayer, If fMLP, IL-8, zymosan-activated plasma (a source of activated complement factor C5a), epithelial cell-derived neutrophil-activating peptide (ENA-78), or growth-regulating oncogene, GRO-alpha, was perfused over these neutrophils, they stopped rolling and rapidly migrated over the monolayer, but did not penetrate it. When HUVEC were treated with 100 U/ml TNF, the majority of adherent neutrophils transmigrated. If neutrophils were treated with fMLP, IL-8, C5a, ENA-78, or GRO-alpha just before perfusion over this HUVEC, transmigration, but not adhesion, was abolished. However, when platelet-activating factor was used to activate neutrophils, migration through HUVEC treated with 100 U/ml TNF was not impaired, and migration through HUVEC treated with 2 U/ml TNF was actually increased. Transmigration required ligation of CXC chemokine receptor-2 on neutrophils, and differential desensitization of this receptor (e.g., by fMLP but not platelet-activating factor) may explain the pattern of disruption of migration. Thus, transmigration may require presentation of the correct activators in the correct sequence, and inappropriate activation (e.g., by systemic activators) could cause pathological accumulation of neutrophils in the vessel lumen.