Transit time of leukocytes rolling through venules controls cytokine-induced inflammatory cell recruitment in vivo
Transit time of leukocytes rolling through venules controls cytokine-induced inflammatory cell recruitment in vivo
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DOI：
10.1172/jci119893
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发表时间：
1998-10-15
影响因子：
15.9
通讯作者：
Ley, K
中科院分区：
文献类型：
--
作者：
Jung, U;Norman, KE;Ley, K
白细胞募集需要白细胞滚动、活化、牢固粘附和迁移。注射促炎细胞因子TNF-α诱导内皮表面上E-选择素、白细胞介素-8和其他粘附分子和化学引诱物的表达。TNF-α处理的CD 18无效小鼠提睾肌小静脉显示白细胞滚动速度增加和白细胞募集效率降低。抗E-选择素的mAb可显著阻断CD 18缺失小鼠而非野生型小鼠的白细胞募集。为了理解这种重叠的粘附事件之前被认为是分开的，我们引入了一个定量分析的效率诱导滚动，滚动转换为粘附，粘附轮回。我们发现，CD 18和E-sdectin合作，以控制白细胞需要滚动通过发炎区域的时间，并将滚动转换为牢固的粘附。白细胞滚动时间，定义为滚动的白细胞通过规定长度的血管段所需的时间，作为确定诱导牢固粘附效率的统一参数出现，这是控制炎症中白细胞募集的限速步骤。我们的结论是，白细胞整合趋化信号，同时滚动沿着内皮表面，直到他们达到一个临界水平的激活，并成为牢固的粘附。
Leukocyte recruitment requires leukocyte rolling, activation, firm adhesion, and transmigration. Injection of the proinflammatory cytokine TNF-alpha induces expression of E-selectin, interleukin-8, and other adhesion molecules and chemoattractants on the endothelial surface. TNF-alpha-treated CD18 null mouse cremaster muscle venules show increased leukocyte rolling velocity and reduced leukocyte recruitment efficiency. Leukocyte recruitment in CD18 null but not wild-type mice is significantly blocked by an mAb to E-selectin. To understand this overlap between adhesion events previously considered separate, we introduce a quantitative analysis of the efficiency of induction of rolling, conversion of rolling to adhesion, and of adhesion to transmigration. We find that CD18 and E-sdectin cooperate to control the time a leukocyte needs to roll through an inflamed area and to convert rolling to firm adhesion. Leukocyte rolling time, defined as the time it takes for a rolling leukocyte to pass through a defined length of a vessel segment, emerges as a unifying parameter determining the efficiency of inducing firm adhesion, which is a rate-limiting step controlling leukocyte recruitment in inflammation. We conclude that leukocytes integrate chemoattractant signals while rolling along the endothelial surface until they reach a critical level of activation and become firmly adherent.