Roflumilast抑制leukocyte-endothelial细胞相互作用,粘附分子的表达和微血管通透性。

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Sanz MJ, Cortijo J,塔哈马,Cerda-Nicolas M, Schatton E, Burgbacher B, Klar J,男高音H, Schudt C, Issekutz AC, Hatzelmann Morcillo EJ

Roflumilast抑制leukocyte-endothelial细胞相互作用,粘附分子的表达和微血管通透性。

Br J杂志。2007年10月,152 (4):481 - 92。Epub 2007 8月20。

PubMed ID

17704822 (在PubMed

]

文摘

背景和目的:本研究解决临床实验的影响PDE4抑制剂roflumilast leukocyte-endothelial细胞相互作用和内皮渗透性体内和体外。实验方法:体内,活体的video-microscopy被用来确定roflumilast汇票对leukocyte-endothelial细胞相互作用的影响和对大鼠肠系膜微血管通透性小静脉。体外,的影响roflumilast N-oxide, roflumilast活性代谢物的人类,和其他PDE4抑制剂对中性粒细胞粘附肿瘤坏死因子α(TNFalpha)激活人类脐静脉内皮细胞(HUVEC), E-selectin表达和thrombin-induced内皮渗透性是评价。流式细胞仪是用于确定roflumilast的影响N-formyl-methionyl-leucyl-phenylalanine (fMLP)全身CD11b upregulation在人类中性粒细胞。主要结果:体内,roflumilast,鉴于前1 h脂多糖(LPS),剂量依赖性降低leukocyte-endothelial细胞相互作用在大鼠肠系膜postcapillary小静脉。它还减少histamine-induced微血管通透性。免疫组织化学分析显示,roflumilast阻止LPS-induced内皮P -和E-selectin表达式。在体外,roflumilast N-oxide concentration-dependently抑制中性粒细胞粘附TNFalpha-activated HUVEC fMLP-stimulated中性粒细胞和CD11b表达。它还减少TNFalpha-induced E-selectin表情HUVEC,当PDE3活动受阻。HUVEC渗透引起的凝血酶被roflumilast concentration-dependently镇压N-oxide。 While roflumilast N-oxide was as potent as roflumilast at inhibiting stimulated endothelial cell and neutrophil functions, both compounds were significantly more potent than the structurally unrelated PDE4 inhibitors, rolipram or cilomilast. CONCLUSIONS AND IMPLICATIONS: These findings further support earlier observations on the inhibition of inflammatory cell influx and protein extravasation by roflumilast in vivo.

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药物

Roflumilast