Yamamoto T, Kajikawa O, Martin T R, Sharar S R, Harlan J M, Winn R K
Pharmaceuticals Laboratory I, Yokohama Research Center, Mitsubishi Chemical Corporation, Japan.
J Immunol. 1998 Nov 15;161(10):5704-9.
Leukocyte emigration and alveolar macrophage-derived cytokines may contribute to lung microvascular injury associated with adult respiratory distress syndrome. We have used mAbs against cell adhesion molecules on leukocytes (anti-CD18 and anti-CD49d) or against IL-8 to investigate these contributions. Intratracheal (i.t.) instillation of LPS (50 microg/kg) caused a significant increase in bronchoalveolar lavage polymorphonuclear leukocytes (PMNs) without an increase in mononuclear cells (MNCs) or an increase in lung permeability. Injection of LPS (10 microg/kg) i.v. at 24 h after i.t. LPS caused significant increases in bronchoalveolar lavage PMNs, MNCs, IL-8, and monocyte chemotactic protein-1, as well as increases in lung permeability. Rabbits that were administered i.t. LPS followed by i.v. LPS and treated with anti-CD18 mAb had a significantly lower lung permeability index and emigration of fewer PMNs but no change in MNC emigration compared with saline treatment. Anti-IL-8 mAb treatment resulted in a significantly lower lung permeability index with no change in PMN emigration compared with no treatment. These results suggest that PMN emigration is necessary but not sufficient for the development of LPS-induced lung injury, and that IL-8 plays a significant role in PMN-dependent lung injury, independent of PMN emigration.
白细胞迁移和肺泡巨噬细胞衍生的细胞因子可能与成人呼吸窘迫综合征相关的肺微血管损伤有关。我们使用了针对白细胞上细胞粘附分子的单克隆抗体（抗CD18和抗CD49d）或针对白细胞介素-8的单克隆抗体来研究这些作用。气管内（i.t.）注入脂多糖（LPS，50微克/千克）导致支气管肺泡灌洗多形核白细胞（PMN）显著增加，而单核细胞（MNC）无增加，肺通透性也无增加。在气管内注入LPS后24小时静脉内（i.v.）注射LPS（10微克/千克），导致支气管肺泡灌洗PMN、MNC、白细胞介素-8和单核细胞趋化蛋白-1显著增加，同时肺通透性增加。先气管内注入LPS，随后静脉内注入LPS并接受抗CD18单克隆抗体治疗的兔子，与生理盐水治疗相比，肺通透性指数显著降低，PMN迁移减少，但MNC迁移无变化。与未治疗相比，抗白细胞介素-8单克隆抗体治疗导致肺通透性指数显著降低，PMN迁移无变化。这些结果表明，PMN迁移对于LPS诱导的肺损伤的发生是必要的，但不是充分的，并且白细胞介素-8在PMN依赖性肺损伤中起重要作用，独立于PMN迁移。
