Rosengren S, Björk J, Smedegård G
Department of Experimental Medicine, Pharmacia AB, University of Uppsala, Sweden.
Lab Invest. 1988 May;58(5):559-64.
The neutrophil granulocyte is considered to play a key role in the inflammatory process, contributing to the increased microvascular permeability and tissue damage seen at inflammatory sites. The mechanism underlying this process is unknown, but studies in vitro using cultured endothelium and blood polymorphonuclear granulocytes (PMNs) point to an involvement of oxygen-free radicals. In this study, we have used the hamster cheek pouch microcirculatory model to evaluate the impact of radical scavenging enzymes, superoxide dismutase (SOD), and catalase on the microvascular inflammatory reactions induced by leukotriene B4 (LTB4), which is known to induce PMN-dependent plasma leakage in this model. The variables studied were leukocyte adhesion in postcapillary venules, macromolecular permeability as leakage of fluorescent dextran, and emigration of PMNs. SOD and catalase were given in high doses as intravenous infusion and also as superfusion over the cheek pouch. All studied variables increased dramatically upon superfusion of LTB4 (4 nM) over the cheek pouch preparation and remained elevated throughout the 30-minute exposure period. Treatment with SOD and/or catalase did not influence this inflammatory response to LTB4. Nor did SOD and catalase influence the plasma leakage and emigration of PMNs caused by superfusion of the synthetic chemotactic peptide, formylmethionylleucylphenylalanine (400 nM) which from other animal models is known to induce a PMN-dependent plasma leakage. Although free radicals might contribute to the tissue damage seen at some inflammatory sites, we conclude that they are not crucially involved in the interaction between the PMN and the microvascular endothelium induced by the inflammatory mediators LTB4 and formylmethionylleucylphenylalanine, and are thus not a prerequisite for PMN-dependent microvascular permeability.
中性粒细胞被认为在炎症过程中起关键作用，导致炎症部位微血管通透性增加和组织损伤。这一过程的潜在机制尚不清楚，但使用培养的内皮细胞和血液多形核粒细胞（PMN）进行的体外研究表明，氧自由基参与其中。在本研究中，我们使用仓鼠颊囊微循环模型来评估自由基清除酶超氧化物歧化酶（SOD）和过氧化氢酶对由白三烯B4（LTB4）诱导的微血管炎症反应的影响，已知在该模型中LTB4可诱导依赖PMN的血浆渗漏。研究的变量包括毛细血管后微静脉中的白细胞黏附、作为荧光葡聚糖渗漏的大分子通透性以及PMN的迁移。SOD和过氧化氢酶以高剂量静脉输注给药，并通过颊囊灌注给药。在颊囊制剂上灌注LTB4（4 nM）后，所有研究变量均显著增加，并在整个30分钟的暴露期内保持升高。用SOD和/或过氧化氢酶治疗并未影响对LTB4的这种炎症反应。SOD和过氧化氢酶也未影响由合成趋化肽甲酰甲硫氨酰亮氨酰苯丙氨酸（400 nM）灌注引起的血浆渗漏和PMN迁移，从其他动物模型可知该趋化肽可诱导依赖PMN的血浆渗漏。尽管自由基可能在某些炎症部位导致组织损伤，但我们得出结论，它们并非关键参与由炎症介质LTB4和甲酰甲硫氨酰亮氨酰苯丙氨酸诱导的PMN与微血管内皮之间的相互作用，因此不是依赖PMN的微血管通透性的先决条件。
