Bless N M, Tojo S J, Kawarai H, Natsume Y, Lentsch A B, Padgaonkar V A, Czermak B J, Schmal H, Friedl H P, Ward P A
Department of Traumatology, University of Freiburg, Germany.
Am J Pathol. 1998 Oct;153(4):1113-22. doi: 10.1016/S0002-9440(10)65655-6.
Using two models of acute lung inflammatory injury in rats (intrapulmonary deposition of immunoglobulin G immune complexes and systemic activation of complement after infusion of purified cobra venom factor), we have analyzed the requirements and patterns for upregulation of lung vascular P-selectin. In the immune complex model, upregulation of P-selectin was defined by Northern and Western blot analysis of lung homogenates, by immunostaining of lung tissue, and by vascular fixation of 125I-labeled anti-P-selectin. P-selectin protein was detected by 1 hour (long before detection of mRNA) and expression was sustained for the next 7 hours, in striking contrast to the pattern of P-selectin expression in the cobra venom factor model, in which upregulation was very transient (within the 1st hour). In the immune complex model, injury and neutrophil accumulation were P-selectin dependent. Upregulation of P-selectin was dependent on an intact complement system, and the presence of blood neutrophils was susceptible to the antioxidant dimethyl sulfoxide and required C5a but not tumor necrosis factor alpha. In contrast, in the cobra venom factor model, upregulation of P-selectin, which is C5a dependent, was also dimethyl sulfoxide sensitive but neutrophil independent. Different mechanisms that may explain why upregulation of lung vascular P-selectin is either transient or sustained are discussed.
我们使用大鼠急性肺炎性损伤的两种模型（免疫球蛋白G免疫复合物的肺内沉积以及注入纯化的眼镜蛇毒因子后补体的全身激活），分析了肺血管P-选择素上调的条件和模式。在免疫复合物模型中，通过对肺匀浆进行Northern和Western印迹分析、对肺组织进行免疫染色以及对125I标记的抗P-选择素进行血管固定来确定P-选择素的上调。P-选择素蛋白在1小时时即可检测到（远早于mRNA的检测），并且在接下来的7小时内持续表达，这与眼镜蛇毒因子模型中P-选择素的表达模式形成鲜明对比，在该模型中上调非常短暂（在第1小时内）。在免疫复合物模型中，损伤和中性粒细胞积聚依赖于P-选择素。P-选择素的上调依赖于完整的补体系统，血液中性粒细胞的存在对抗氧化剂二甲基亚砜敏感，并且需要C5a，但不需要肿瘤坏死因子α。相比之下，在眼镜蛇毒因子模型中，依赖于C5a的P-选择素上调对二甲基亚砜也敏感，但不依赖于中性粒细胞。文中讨论了可能解释肺血管P-选择素上调为何是短暂或持续的不同机制。
