Guo Ren-Feng, Ward Peter A
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Free Radic Biol Med. 2002 Aug 1;33(3):303-10. doi: 10.1016/s0891-5849(02)00823-7.
Neutrophil trafficking in lung involves transendothelial migration, migration in tissue interstitium, and transepithelial migration. In a rat model of IgG immune complex-induced lung injury, it was demonstrated that neutrophil emigration involves regulatory mechanisms including complement activation, cytokine regulation, chemokine production, activation of adhesion molecules, and their respective counter receptors. The process is presumably initiated and modulated by the production of early response cytokines and chemokines from lung cells, especially from alveolar macrophages. TNF-alpha and IL-1 up-regulate intracellular adhesion molecule-1 (ICAM-1) and E-selectin, setting the stage for neutrophil migration through endothelium. The CXC chemokines, such as macrophage inflammatory protein (MIP)-2 and cytokine-inducible neutrophil chemoattractant (CINC), constitute chemokine gradient to orchestrate neutrophil migration in lung. Complement activation induced by IgG immune complex deposition is another important event leading to neutrophil accumulation in lung. Complement activation product C5a not only plays an important role in chemoattracting neutrophils into lung, but regulates adhesion molecules, chemokines, and cytokines expression. In addition, oxidative stress may regulate neutrophil accumulation in lung by modulation of adhesion molecule activation and chemokine production. In this review, we focus on the current knowledge of the mechanisms leading to accumulation of neutrophils during acute lung injury.
中性粒细胞在肺内的迁移涉及跨内皮迁移、在组织间质中的迁移以及跨上皮迁移。在IgG免疫复合物诱导的肺损伤大鼠模型中，已证实中性粒细胞的渗出涉及多种调节机制，包括补体激活、细胞因子调节、趋化因子产生、黏附分子激活及其相应的反受体。该过程可能由肺细胞，特别是肺泡巨噬细胞产生的早期反应细胞因子和趋化因子启动并调节。肿瘤坏死因子-α（TNF-α）和白细胞介素-1（IL-1）上调细胞间黏附分子-1（ICAM-1）和E-选择素，为中性粒细胞通过内皮迁移奠定基础。CXC趋化因子，如巨噬细胞炎性蛋白（MIP）-2和细胞因子诱导的中性粒细胞趋化因子（CINC），构成趋化因子梯度，以协调中性粒细胞在肺内的迁移。IgG免疫复合物沉积诱导的补体激活是导致中性粒细胞在肺内积聚的另一个重要事件。补体激活产物C5a不仅在将中性粒细胞吸引到肺内方面起重要作用，还调节黏附分子、趋化因子和细胞因子的表达。此外，氧化应激可能通过调节黏附分子激活和趋化因子产生来调节中性粒细胞在肺内的积聚。在本综述中，我们重点关注急性肺损伤期间导致中性粒细胞积聚的机制的当前知识。
