Annexin 1-deficient neutrophils exhibit enhanced transmigration in vivo and increased responsiveness in vitro
Annexin 1-deficient neutrophils exhibit enhanced transmigration in vivo and increased responsiveness in vitro
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DOI：
10.1189/jlb.0405206
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发表时间：
2005-09-01
影响因子：
5.5
通讯作者：
Perretti, M
中科院分区：
文献类型：
--
作者：
Chatterjee, BE;Yona, S;Perretti, M
内源性抗炎介质膜联蛋白1（AnxA 1）在控制多形核白细胞（PMN）的运输和激活的作用，解决了使用最近产生的AnxA 1空小鼠。在酵母多糖腹膜炎模型中，AnxA 1基因敲除小鼠与野生型同窝小鼠相比，PMN募集程度更高（50-70%），这与F4/80（+）细胞数量减少有关。酵母多糖（6小时时间点）发炎的提睾肌微循环的活体显微镜分析表明，在AnxA 1基因敲除小鼠中，白细胞迁移的程度更大，但不滚动或粘附。实时分析的提睾肌微循环没有显示自发激活的情况下，AnxA 1，然而，灌流与直接作用的PMN激活剂（1 nM血小板激活因子）显示了一个微妙的，但显着增加白细胞迁移，但不滚动或粘附，在这个基因型。微循环的变化并不继发于血流动力学参数的改变。AnxA 1空中性粒细胞的表型进行了研究，在两个体外细胞活化（CD 11b膜表达和趋化性）的测定：获得的数据表明，无论使用的刺激更高程度的细胞反应。总之，我们已经使用了炎症协议和体外试验的组合，以解决特定的反调节作用的内源性AnxA 1，证明其对中性粒细胞活化的抑制控制和随之而来的影响发炎的微循环。
The role of the endogenous anti-inflammatory mediator annexin 1 (AnxA1) in controlling polymorphonuclear leukocyte (PMN) trafficking and activation was addressed using the recently generated AnxA1 null mouse. In the zymosan peritonitis model, AnxA1 null mice displayed a higher degree (50-70%) of PMN recruitment compared with wild-type littermate mice, and this was associated with reduced numbers of F4/80(+) cells. Intravital microscopy analysis of the cremaster microcirculation inflamed by zymosan (6 h time-point) indicated a greater extent of leukocyte emigration, but not rolling or adhesion, in AnxA1 null mice. Real-time analysis of the cremaster microcirculation did not show spontaneous activation in the absence of AnxA1; however, superfusion with a direct-acting PMN activator (1 nM platelet-activating factor) revealed a subtle yet significant increase in leukocyte emigration, but not rolling or adhesion, in this genotype. Changes in the microcirculation were not secondary to alterations in hemodynamic parameters. The phenotype of the AnxA1 null PMN was investigated in two in vitro assays of cell activation (CD11b membrane expression and chemotaxis): the data obtained indicated a higher degree of cellular responses irrespective of the stimulus used. In conclusion, we have used a combination of inflammatory protocols and in vitro assays to address the specific counter-regulatory role of endogenous AnxA1, demonstrating its inhibitory control on PMN activation and the consequent impact on the inflamed microcirculation.