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肿瘤坏死因子-α诱导小鼠提睾肌小动脉中选择素介导的白细胞滚动。

TNF-alpha induces selectin-mediated leukocyte rolling in mouse cremaster muscle arterioles.

作者信息

Kunkel E J, Jung U, Ley K

机构信息

Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville 22908, USA.

出版信息

Am J Physiol. 1997 Mar;272(3 Pt 2):H1391-400. doi: 10.1152/ajpheart.1997.272.3.H1391.

DOI:10.1152/ajpheart.1997.272.3.H1391
PMID:9087616
Abstract

Leukocyte rolling is commonly restricted to venules and mediated by selectins expressed both on leukocytes (L-selectin) and the vascular endothelium (P- and E-selectin). We show here that 2- to 3-h tumor necrosis factor-alpha (TNF-alpha) stimulation of the mouse cremaster muscle induces rolling in arterioles (diameters 30-70 microm; wall shear rates 225-1,770 s(-1)). Weak P-selectin expression was detected on arteriolar endothelium of TNF-alpha-stimulated cremaster muscles. No rolling was observed in arterioles smaller than 30 microm (wall shear rates 1,500-3,250 s(-1)). The arteriolar rolling flux fraction in wild-type mice averaged approximately 5% and rolling was blocked by the P-selectin monoclonal antibody (MAb) RB40.34. Rolling in L- and E-selectin-deficient mice was similar to that in wild-type mice and was also blocked by the MAb RB40.34. Rolling was completely absent in arterioles of P-selectin-deficient mice. The average rolling velocity in arterioles of wild-type and L-selectin-deficient mice was approximately 50 microm/s but increased to approximately 110 microm/s in E-selectin-deficient mice and after injection of the blocking E-selectin MAb 9A9 in wild-type mice. We conclude that TNF-alpha treatment induces P-selectin-dependent rolling in arterioles that requires E-selectin for rolling at normal velocities.

摘要

白细胞滚动通常局限于微静脉,由白细胞(L-选择素)和血管内皮(P-选择素和E-选择素)上表达的选择素介导。我们在此表明,对小鼠提睾肌进行2至3小时的肿瘤坏死因子-α(TNF-α)刺激可诱导小动脉(直径30 - 70微米;壁剪切速率225 - 1770 s⁻¹)中的滚动。在TNF-α刺激的提睾肌的小动脉内皮上检测到弱P-选择素表达。在直径小于30微米(壁剪切速率1500 - 3250 s⁻¹)的小动脉中未观察到滚动。野生型小鼠中小动脉的滚动通量分数平均约为5%,滚动被P-选择素单克隆抗体(MAb)RB40.34阻断。L-选择素和E-选择素缺陷小鼠中的滚动与野生型小鼠相似,也被MAb RB40.34阻断。P-选择素缺陷小鼠的小动脉中完全没有滚动。野生型和L-选择素缺陷小鼠小动脉中的平均滚动速度约为50微米/秒,但在E-选择素缺陷小鼠中以及在野生型小鼠中注射阻断性E-选择素单克隆抗体9A9后,滚动速度增加到约110微米/秒。我们得出结论,TNF-α处理可诱导小动脉中P-选择素依赖性滚动,正常速度的滚动需要E-选择素。

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