CXCR2- and E-selectin-induced neutrophil arrest during inflammation in vivo.
CXCR2- and E-selectin-induced neutrophil arrest during inflammation in vivo.
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DOI：
10.1084/jem.20040424
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发表时间：
2004-10-04
影响因子：
15.3
通讯作者：
Ley, K
中科院分区：
文献类型：
--
作者：
Smith, ML;Olson, TS;Ley, K
导致整合素活化和炎症小静脉中滚动中性粒细胞的牢固停滞的信号事件尚未阐明。体外试验表明，E-选择素和趋化因子都可以触发滚动中性粒细胞的停滞，但E-选择素−/−小鼠在发炎的小静脉中具有正常水平的粘附中性粒细胞。为了测试体内趋化因子诱导的中性粒细胞停滞是否可以通过阻断E-选择素来揭示，我们研究了注射E-选择素阻断单克隆抗体（mAb）9A 9的肿瘤坏死因子（TNF）-α治疗的CXCR 2 −/−或野生型（WT）小鼠炎症提睾肌小静脉中的中性粒细胞粘附。为了阻断趋化因子受体信号传导，我们研究了静脉注射百日咳毒素（PTx）的E-选择素−/−或WT小鼠。在CXCR 2 −/−、E-选择素−/−、PTX处理的WT或mAb 9A 9处理的WT小鼠中，神经元粘附未发生变化。然而，TNF-α诱导的中性粒细胞粘附在用PTx处理的E-选择素−/−小鼠中几乎完全消除，并且在用E-选择素阻断mAb处理的CXCR 2 −/−小鼠中显著降低。在巯基乙酸盐诱导的腹膜炎中，PTx治疗阻断了中性粒细胞募集到E-选择素−/−小鼠的腹膜中，但在WT动物中仅具有部分作用。这些数据表明，E-选择素和趋化因子介导的逮捕机制是重叠的，在这个模型中，并确定CXCR 2作为一个重要的中性粒细胞逮捕趋化因子在体内。
The signaling events leading to the activation of integrins and firm arrest of rolling neutrophils in inflamed venules have yet to be elucidated. In vitro assays suggest that both E-selectin and chemokines can trigger arrest of rolling neutrophils, but E-selectin−/− mice have normal levels of adherent neutrophils in inflamed venules. To test whether chemokine-induced neutrophil arrest in vivo can be unmasked by blocking E-selectin, we investigated neutrophil adhesion in inflamed cremaster muscle venules in tumor necrosis factor (TNF)-α–treated CXCR2−/− or wild-type (WT) mice injected with E-selectin blocking monoclonal antibody (mAb) 9A9. To block chemokine receptor signaling, we investigated E-selectin−/− or WT mice treated with pertussis toxin (PTx) intravenously. Neutrophil adhesion was unchanged in CXCR2−/−, E-selectin−/−, PTx-treated WT, or mAb 9A9–treated WT mice. However, TNF-α–induced neutrophil adhesion was almost completely abrogated in E-selectin−/− mice treated with PTx and significantly reduced in CXCR2−/− mice treated with the E-selectin blocking mAb. In thioglycollate-induced peritonitis, PTx treatment blocked neutrophil recruitment into the peritoneum of E-selectin−/− mice, but had only a partial effect in WT animals. These data show that E-selectin– and chemokine-mediated arrest mechanisms are overlapping in this model and identify CXCR2 as an important neutrophil arrest chemokine in vivo.
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DOI：
10.1084/jem.190.12.1769
发表时间：
1999-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Yang J;Hirata T;Croce K;Merrill-Skoloff G;Tchernychev B;Williams E;Flaumenhaft R;Furie BC;Furie B
通讯作者：
Furie B
影响因子：
56.9
作者：
Campbell, JJ;Hedrick, J;Butcher, EC
通讯作者：
Butcher, EC
影响因子：
15.9
作者：
Jung, U;Norman, KE;Ley, K
通讯作者：
Ley, K
DOI：
10.1083/jcb.136.3.707
发表时间：
1997-02-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Zöllner O;Lenter MC;Blanks JE;Borges E;Steegmaier M;Zerwes HG;Vestweber D
通讯作者：
Vestweber D
影响因子：
32.4
作者：
Constantin, G;Majeed, M;Laudanna, C
通讯作者：
Laudanna, C