NITRIC-OXIDE, BUT NOT INTERLEUKIN-1, MEDIATES THE LOCAL BLOOD-FLOW RESPONSE TO LIPOPOLYSACCHARIDE IN RABBIT SKIN
NITRIC-OXIDE, BUT NOT INTERLEUKIN-1, MEDIATES THE LOCAL BLOOD-FLOW RESPONSE TO LIPOPOLYSACCHARIDE IN RABBIT SKIN
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DOI：
10.1016/0014-2999(93)90971-j
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发表时间：
1993-08-03
影响因子：
5
通讯作者：
WARREN, JB
中科院分区：
文献类型：
--
作者：
PONS, F;WILLIAMS, TJ;WARREN, JB
脂多糖可以模拟革兰氏阴性菌的炎症反应的许多方面。在家兔和大鼠皮肤中，脂多糖诱导中性粒细胞积聚和血流量增加。白细胞介素-1，肿瘤坏死因子-α和血管扩张剂，一氧化氮（NO）已被牵连在生物反应脂多糖和革兰氏阴性菌。在本研究中，我们的特点是局部血管反应E。大肠杆菌内毒素对家兔皮肤的影响，并研究其对蛋白质合成、NO、白细胞介素1和中性粒细胞的依赖性。通过用激光多普勒流量计测量局部血流的变化来确定局部血管对皮内注射脂多糖的反应。注射脂多糖（3、10和30 μ g/部位）诱导血流量呈剂量相关性增加，在2 h时达到最大值。同时注射放线菌素D（4 × 10（-9）mol/部位）可消除对10 μ g/部位脂多糖的反应，N（G）-硝基-L-精氨酸甲酯（10（-7）mol/部位）可使反应降低60%，地塞米松（2 mg/kg，静脉注射）预处理的家兔可使反应降低82%。然而，脂多糖诱导的血流量增加不受重组人白细胞介素-1受体拮抗剂（7.0 × 10（-11）mol/部位）或全身中性粒细胞耗竭的影响。这些结果表明，脂多糖导致延迟的兔皮肤微血管的血管舒张，这取决于蛋白质的合成，并涉及部分NO的释放。然而，这种反应不依赖于白细胞介素-1或中性粒细胞。脂多糖的血管舒张作用可能涉及通过独立于白细胞介素-1的机制在血管壁中表达诱导型NO合酶。
Lipopolysaccharide can mimic many aspects of the inflammatory response to gram-negative bacteria. In rabbit and rat skin, lipopolysaccharide induces neutrophil accumulation and an increase in blood flow. Interleukin-1, tumor necrosis factor-alpha and the vasodilator, nitric oxide (NO) have been implicated in the biological responses to lipopolysaccharide and gram-negative bacteria. In the present study, we characterized the local vascular response to E. coli lipopolysaccharide in rabbit skin and investigated its dependence on de novo protein synthesis, NO, interleukin-1 and neutrophils. The local vascular response to the intradermal injection of lipopolysaccharide was determined by measuring changes in local blood flow with a laser-Doppler flowmeter. Injections of lipopolysaccharide (3, 10 and 30 mug/site) induced a dose-related increase in blood flow, with a maximum at 2 h. The response to 10 mug/site lipopolysaccharide was abolished by co-injection of actinomycin D (4 x 10(-9)) mol/site), reduced by 60% by N(G)-nitro-L-arginine methyl ester (10(-7) mol/site) and suppressed by 82% in rabbits pretreated with dexamethasone (2 mg/kg, i.v.). However, the lipopolysaccharide-induced increase in blood flow was not affected by co-injection of recombinant human interleukin-1 receptor antagonist (7.0 x 10(-11) mol/site) or by systemic neutrophil depletion. These results demonstrate that lipopolysaccharide causes delayed vasodilatation of the rabbit cutaneous microvasculature which depends on protein synthesis and involves in part the release of NO. However, this response does not depend on interleukin-1 or neutrophils. The vasodilator effect of lipopolysaccharide may involve the expression of the inducible form of NO synthase in the vessel wall, through a mechanism independent of interleukin-1.