Proinflammatory activities of S100: Proteins S10OA8, S10OA9, and S100A8/A9 induce neutrophil chemotaxis and adhesion
Proinflammatory activities of S100: Proteins S10OA8, S10OA9, and S100A8/A9 induce neutrophil chemotaxis and adhesion
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DOI：
10.4049/jimmunol.170.6.3233
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发表时间：
2003-03-15
影响因子：
4.4
通讯作者：
Tessier, PA
中科院分区：
文献类型：
--
作者：
Ryckman, C;Vandal, K;Tessier, PA
S100A8 和 S100A9 是小型钙结合蛋白，在中性粒细胞和单核细胞胞浆中高度表达，并且在炎症条件下在细胞外环境中以高水平存在。 Although reports have proposed a proinflammatory role for these proteins, their extracellular activity remains controversial.在本研究中，我们报告S10OA8、S100A9和S100A8/A9在10(-12)-10(-9) M浓度下引起中性粒细胞趋化性。S100A8、S100A9和S100A8/A9刺激L-选择素脱落，上调和激活Mac-1，并在体外诱导中性粒细胞与纤维蛋白原粘附。 Neutralization with Ab showed that this adhesion was mediated by Mac-1. Neutrophil adhesion was also associated with an increase in intracellular calcium levels. However, neutrophil activation by S10OA8, S100A9, and S100A8/A9 did not induce actin polymerization.最后，将 S100A8、S100A9 或 S100A8/A9 注射到小鼠气囊模型中，导致中性粒细胞快速、短暂的积累，证实了它们在体内的活性。这些研究 1) 表明 S100A8、S100A9 和 S100A8/A9 是中性粒细胞的有效刺激剂，2) 强烈表明这些蛋白质参与中性粒细胞向炎症部位的迁移。
S100A8 and S100A9 are small calcium-binding proteins that are highly expressed in neutrophil and monocyte cytosol and are found at high levels in the extracellular milieu during inflammatory conditions. Although reports have proposed a proinflammatory role for these proteins, their extracellular activity remains controversial. In this study, we report that S10OA8, S100A9, and S100A8/A9 caused neutrophil chemotaxis at concentrations of 10(-12)-10(-9) M. S100A8, S100A9, and S100A8/A9 stimulated shedding of L-selectin, up-regulated and activated Mac-1, and induced neutrophil adhesion to fibrinogen in vitro. Neutralization with Ab showed that this adhesion was mediated by Mac-1. Neutrophil adhesion was also associated with an increase in intracellular calcium levels. However, neutrophil activation by S10OA8, S100A9, and S100A8/A9 did not induce actin polymerization. Finally, injection of S100A8, S100A9, or S100A8/A9 into a murine air pouch model led to rapid, transient accumulation of neutrophils confirming their activities in vivo. These studies 1) show that S100A8, S100A9, and S100A8/A9 are potent stimulators of neutrophils and 2) strongly suggest that these proteins are involved in neutrophil migration to inflammatory sites.