Vandal Karen, Rouleau Pascal, Boivin Annie, Ryckman Carle, Talbot Mariève, Tessier Philippe A
Centre de Recherche en Infectiologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Université Laval, 2705 Boulevard Laurier, Sainte-Foy, Québec, Canada G1V 4G2.
J Immunol. 2003 Sep 1;171(5):2602-9. doi: 10.4049/jimmunol.171.5.2602.
Recently, proinflammatory activities had been described for S100A8 and S100A9, two proteins found at inflammatory sites and within the neutrophil cytoplasm. In this study, we investigated the role of these proteins in neutrophil migration in vivo in response to LPS. LPS was injected into the murine air pouch, which led to the release of S100A8, S100A9, and S100A8/A9 in the pouch exudates that preceded accumulation of neutrophils. Passive immunization against S100A8 and S100A9 led to a 52% inhibition of neutrophil migration in response to LPS at 3 h postinjection. Injection of LPS was also associated with an increase in peripheral blood neutrophils and the presence in serum of S100A9 and S100A8/A9. Intravenous injection of S100A8, S100A9, or S100A8/A9 augmented the number of circulating neutrophils and diminished the number of neutrophils in the bone marrow, demonstrating that S100A8 and S100A9 induced the mobilization of neutrophils from the bone marrow to the blood. Finally, passive immunization with anti-S100A9 inhibited the neutrophilia associated with LPS injection in the air pouch. These results suggest that S100A8 and S100A9 play a role in the inflammatory response to LPS by inducing the release of neutrophils from the bone marrow and directing their migration to the inflammatory site.
最近，已报道炎症部位及中性粒细胞胞质中发现的两种蛋白S100A8和S100A9具有促炎活性。在本研究中，我们调查了这些蛋白在体内对脂多糖（LPS）反应中中性粒细胞迁移的作用。将LPS注入小鼠气袋，导致在中性粒细胞积聚之前，气袋渗出液中释放出S100A8、S100A9和S100A8/A9。对S100A8和S100A9进行被动免疫，导致注射后3小时对LPS反应的中性粒细胞迁移受到52%的抑制。注射LPS还与外周血中性粒细胞增加以及血清中出现S100A9和S100A8/A9有关。静脉注射S100A8、S100A9或S100A8/A9可增加循环中性粒细胞数量，并减少骨髓中的中性粒细胞数量，表明S100A8和S100A9诱导中性粒细胞从骨髓动员至血液。最后，用抗S100A9进行被动免疫可抑制气袋中与LPS注射相关的中性粒细胞增多。这些结果表明，S100A8和S100A9通过诱导中性粒细胞从骨髓释放并引导其迁移至炎症部位，在对LPS的炎症反应中发挥作用。
