Maris Nico A, van der Sluijs Koenraad F, Florquin Sandrine, de Vos Alex F, Pater Jennie M, Jansen Henk M, van der Poll Tom
Department of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Am J Physiol Lung Cell Mol Physiol. 2004 Jun;286(6):L1122-8. doi: 10.1152/ajplung.00125.2003. Epub 2004 Jan 16.
Lipopolysaccharide is ubiquitously present in the environment. To determine the effect of salmeterol, a long-acting beta(2)-receptor agonist, on lipopolysaccharide-induced lung inflammation, mice received lipopolysaccharide (10 microg) intranasally with or without salmeterol intraperitoneally (5 mg/kg) 30 min earlier and 12 h thereafter. Salmeterol dose- and time-dependently inhibited the lipopolysaccharide-induced influx of neutrophils into bronchoalveolar lavage fluid and lung tissue, and these pulmonary neutrophils displayed a reduced expression of CD11b at their surface. To determine the contribution of the salmeterol effect on neutrophil CD11b in the attenuated neutrophil recruitment, we treated mice intranasally exposed to lipopolysaccharide with salmeterol with or without a blocking anti-CD11b antibody. Anti-CD11b profoundly reduced lipopolysaccharide-induced neutrophil influx in bronchoalveolar lavage fluid, an effect that was modestly enhanced by concurrent salmeterol treatment. These data suggest that salmeterol inhibits lipopolysaccharide-induced neutrophil recruitment to the lungs by a mechanism that possibly in part is mediated by an effect on neutrophil CD11b.
脂多糖在环境中广泛存在。为了确定长效β₂受体激动剂沙美特罗对脂多糖诱导的肺部炎症的影响，小鼠在鼻内给予脂多糖（10微克），在给药前30分钟及给药后12小时腹腔内给予或不给予沙美特罗（5毫克/千克）。沙美特罗剂量和时间依赖性地抑制脂多糖诱导的中性粒细胞流入支气管肺泡灌洗液和肺组织，并且这些肺内中性粒细胞表面的CD11b表达降低。为了确定沙美特罗对中性粒细胞CD11b的作用在减弱中性粒细胞募集中的贡献，我们用或不用抗CD11b阻断抗体处理经鼻暴露于脂多糖的小鼠并给予沙美特罗。抗CD11b显著降低了脂多糖诱导的支气管肺泡灌洗液中的中性粒细胞流入，同时给予沙美特罗治疗可适度增强这一作用。这些数据表明，沙美特罗通过一种可能部分由对中性粒细胞CD11b的作用介导的机制抑制脂多糖诱导的中性粒细胞向肺部募集。
