Effects of LEX032, a novel recombinant serine protease inhibitor, on N(G)-nitro-L-arginine methyl ester induced leukocyte-endothelial cell interactions.
Effects of LEX032, a novel recombinant serine protease inhibitor, on N(G)-nitro-L-arginine methyl ester induced leukocyte-endothelial cell interactions.
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LEX032（一种新型重组丝氨酸蛋白酶抑制剂）对 N(G)-硝基-L-精氨酸甲酯诱导的白细胞-内皮细胞相互作用的影响。
DOI：
10.1016/s0014-2999(98)00521-4
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发表时间：
1998
影响因子：
5
通讯作者：
Lefer,AM
中科院分区：
文献类型：
--
作者：
Bains,AS;Scalia,R;Lefer,AM
我们利用大鼠肠系膜的活体显微镜检查，研究了 LEX032（一种新型丝氨酸蛋白酶抑制剂）对 NG-硝基-L-精氨酸甲酯 (L-NAME) 诱导的体内白细胞-内皮相互作用的影响。与灌注 Krebs-Henseleit (K-H) 溶液的对照大鼠相比，向大鼠肠系膜灌注 50 μM l-NAME（一种一氧化氮 (NO) 抑制剂）90 分钟，导致白细胞滚动、白细胞粘附和白细胞迁移显着且呈时间依赖性增加。然而，对l-NAME灌注大鼠全身给予LEX032（15 mg/kg推注，然后每小时输注15 mg/kg）显着减弱了白细胞沿着大鼠肠系膜小静脉内皮的滚动和粘附，并且还抑制了白细胞通过微血管内皮壁的迁移。此外，全身施用 LEX032 后，平均动脉血压或局部静脉剪切率没有观察到显着变化。我们的数据表明，LEX032 对丝氨酸蛋白酶的全身抑制可减少因抑制 NO 合成而引起的增强的白细胞-内皮相互作用。这些结果还解释了丝氨酸蛋白酶抑制剂在缺血再灌注和其他炎症状态中发挥的一些有益作用。
We studied the effects of LEX032, a novel serine protease inhibitor, on NG-nitro-l-arginine methyl ester (l-NAME) induced leukocyte–endothelium interactions in vivo, utilizing intravital microscopy of the rat mesentery. Superfusion of the rat mesentery with 50 μM l-NAME, a nitric oxide (NO) inhibitor, for 90 min resulted in a significant and time-dependent increase in leukocyte rolling, leukocyte adherence, and transmigration of leukocytes, compared to control rats superfused with Krebs–Henseleit (K–H) solution. However, systemic administration of LEX032 (15 mg/kg bolus injection followed by a 15 mg/kg per hour infusion) to l-NAME superfused rats significantly attenuated leukocyte rolling and adherence along the venular endothelium of the rat mesentery, and also inhibited transmigration of leukocytes through the microvascular endothelial wall. Moreover, no significant changes were observed in mean arterial blood pressure or local venular shear rates following systemic administration of LEX032. Our data demonstrate that systemic inhibition of serine proteases by LEX032 reduces enhanced leukocyte–endothelium interactions provoked by inhibition of NO synthesis. These results also explain some of the beneficial effects exerted by serine protease inhibitors in ischemia-reperfusion and other inflammatory states.