Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF.
Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF.
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DOI：
10.1084/jem.20132413
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发表时间：
2014-06-30
期刊：
影响因子：
--
通讯作者：
Nourshargh S
中科院分区：
文献类型：
--
作者：
Finsterbusch M;Voisin MB;Beyrau M;Williams TJ;Nourshargh S
粘附的中性粒细胞响应于化学引诱物在内皮细胞连接附近释放TNF以介导微血管渗漏。微血管血浆蛋白渗漏是炎症反应的重要组成部分，并在局部宿主防御和组织修复中发挥重要作用。介质如组胺和缓激肽直接作用于微静脉以增加内皮细胞（EC）连接的通透性。中性粒细胞趋化因子也诱导渗漏，这是一种依赖于中性粒细胞粘附于EC的反应，但其潜在机制已被证明是难以捉摸的。通过应用共聚焦活体显微镜的小鼠提睾肌，我们表明，中性粒细胞释放TNF时，在EC交界处密切接近的化学引诱剂。在体外，粘附于ICAM-1或ICAM-2的中性粒细胞响应于LTB 4、C5 a和KC而迅速释放TNF。此外，在TNFR-/-小鼠中，中性粒细胞对提睾肌或背部皮肤给予的化学引诱剂反应正常积聚，但中性粒细胞依赖性血浆蛋白渗漏被消除。在白细胞TNF缺陷的嵌合小鼠中获得了类似的结果。局部注射TNF阻断抗体也能够抑制嗜酸性粒细胞依赖的血浆渗漏，但对缓激肽诱导的反应没有影响。结果表明，TNF介导嗜中性粒细胞依赖性微血管渗漏。这种机制可能有助于TNF抑制剂在炎症性疾病中的作用，并表明可能在危及生命的急性水肿中应用。
Adherent neutrophils responding to chemoattractants release TNF in proximity of endothelial cell junctions to mediate microvascular leakage. Microvascular plasma protein leakage is an essential component of the inflammatory response and serves an important function in local host defense and tissue repair. Mediators such as histamine and bradykinin act directly on venules to increase the permeability of endothelial cell (EC) junctions. Neutrophil chemoattractants also induce leakage, a response that is dependent on neutrophil adhesion to ECs, but the underlying mechanism has proved elusive. Through application of confocal intravital microscopy to the mouse cremaster muscle, we show that neutrophils responding to chemoattractants release TNF when in close proximity of EC junctions. In vitro, neutrophils adherent to ICAM-1 or ICAM-2 rapidly released TNF in response to LTB4, C5a, and KC. Further, in TNFR−/− mice, neutrophils accumulated normally in response to chemoattractants administered to the cremaster muscle or dorsal skin, but neutrophil-dependent plasma protein leakage was abolished. Similar results were obtained in chimeric mice deficient in leukocyte TNF. A locally injected TNF blocking antibody was also able to inhibit neutrophil-dependent plasma leakage, but had no effect on the response induced by bradykinin. The results suggest that TNF mediates neutrophil-dependent microvascular leakage. This mechanism may contribute to the effects of TNF inhibitors in inflammatory diseases and indicates possible applications in life-threatening acute edema.
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影响因子：
20.1
作者：
Naikawadi RP;Cheng N;Vogel SM;Qian F;Wu D;Malik AB;Ye RD
通讯作者：
Ye RD
DOI：
10.1096/fj.11-196220
发表时间：
2012-03
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Colom B;Poitelon Y;Huang W;Woodfin A;Averill S;Del Carro U;Zambroni D;Brain SD;Perretti M;Ahluwalia A;Priestley JV;Chavakis T;Imhof BA;Feltri ML;Nourshargh S
通讯作者：
Nourshargh S
DOI：
10.1083/jcb.200907135
发表时间：
2010-03-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cain RJ;Vanhaesebroeck B;Ridley AJ
通讯作者：
Ridley AJ
影响因子：
4.8
作者：
Di Gennaro, Antonio;Kenne, Ellinor;Haeggstrom, Jesper Z.
通讯作者：
Haeggstrom, Jesper Z.
影响因子：
15.9
作者：
HUBER, AR;WEISS, SJ
通讯作者：
WEISS, SJ