Grimminger F, Kreusler B, Schneider U, Becker G, Seeger W
Department of Internal Medicine, Justus-Liebig University, Giessen, FRG.
J Immunol. 1990 Mar 1;144(5):1866-72.
Profile and quantity of leukotriene (LT) and hydroxyeicosatetraenoic acid (HETE) generation upon selective stimulation of isolated polymorphonuclear neutrophils (PMN) compared with neutrophils in a model of pulmonary leukostasis were investigated. Freshly prepared human PMN (2 x 10(8) were injected into the pulmonary artery of isolated, ventilated, and bloodfree perfused rabbit lungs, resulting in nearly quantitative sticking in the microvasculature. The sequestered neutrophils and, in parallel, aliquots of isolated PMN were stimulated with mAb in the presence of C, known to activate PMN arachidonate metabolism via formation of membrane attack complexes. In the isolated cells, a typical LT profile including LTB4 and its omega-oxidation products, 5-HETE and nonenzymatic hydrolysis products of LTA4 was evoked. The latter indicate secretion of LTA4 in considerable amounts. In the model of pulmonary leukostasis, no nonenzymatic LTA4-derivatives were detected, coincident with a predominance of cysteinyl-LT. This finding gives indirect evidence for an efficient LTA4-transfer between PMN feeder cells and vascular acceptor cells with glutathione-S-transferase activity. Moreover, a threefold increase in the total amount of LTA4-derived products was noted in the model of leukostasis, paralleled by a marked decrease in 5-HETE liberation. This effect was further enhanced by inhibition of lung cyclooxygenase. These findings were corroborated in a homologous system, in which rabbit PMN, sticking in the rabbit lung microvasculature, were stimulated with calcium-ionophore A23187. Collectively, these data suggest a complex interaction between microvascular tissue and adhering neutrophils in LT synthesis, involving transcellular LTA4-shift, modulation of the PMN 5-lipoxygenase pathway, and amplification of LT generation. These findings may be relevant for inflammatory events with neutrophils involved.
研究了在肺白细胞淤滞模型中，与中性粒细胞相比，选择性刺激分离的多形核中性粒细胞（PMN）时白三烯（LT）和羟基二十碳四烯酸（HETE）的生成概况和数量。将新鲜制备的人PMN（2×10⁸）注入离体、通气且无血灌注的兔肺肺动脉，导致几乎定量地黏附于微血管。在补体（C）存在下，用单克隆抗体（mAb）刺激隔离的中性粒细胞以及平行的分离PMN等分试样，已知补体通过形成膜攻击复合物激活PMN花生四烯酸代谢。在分离的细胞中，诱发了典型的LT概况，包括LTB4及其ω-氧化产物、5-HETE和LTA4的非酶促水解产物。后者表明有大量LTA4分泌。在肺白细胞淤滞模型中，未检测到非酶促LTA4衍生物，同时半胱氨酰-LT占主导。这一发现间接证明了PMN供体细胞与具有谷胱甘肽-S-转移酶活性的血管受体细胞之间存在有效的LTA4转移。此外，在白细胞淤滞模型中，LTA4衍生产物的总量增加了三倍，同时5-HETE释放显著减少。肺环氧化酶的抑制进一步增强了这种效应。在同源系统中证实了这些发现，即用钙离子载体A23187刺激黏附于兔肺微血管的兔PMN。总体而言，这些数据表明微血管组织与黏附的中性粒细胞在LT合成中存在复杂的相互作用，涉及跨细胞LTA4转移、PMN Ⅴ-脂氧合酶途径的调节以及LT生成的放大。这些发现可能与涉及中性粒细胞的炎症事件相关。
