Alstergren Per, Zhu Baoqian, Glogauer Michael, Mak Tak W, Ellen Richard P, Sodek Jaro
CIHR Group in Matrix Dynamics, Faculty of Dentistry, University of Toronto, Toronto, Canada M5S 3E2.
Cell Immunol. 2004 Sep-Oct;231(1-2):146-57. doi: 10.1016/j.cellimm.2005.01.007.
The importance of CD44 in murine neutrophil chemotaxis was studied in a Zigmond chamber. WT neutrophils polarized more rapidly and more extensively than CD44-/- neutrophils, which showed slow random migration and reduced activation of RhoA. CD44+/- neutrophils polarized more slowly, formed fewer directionally polarized cells, and migrated more slowly than WT cells. Antibodies to CD44 decreased polarization of WT neutrophils and reduced directed migration but not migration speed, indicating that CD44 mediates chemotactic signaling and migration through different pathways, while a hyaluronate substratum markedly reduced both the speed and directed migration of WT cells. In contrast to macrophages, the level of cell surface CD44 in neutrophils was not affected by osteopontin expression and CD44 did not co-localize with osteopontin. In polarized neutrophils, CD44 was enriched in uropods while cortical actin was predominant at the leading edge. Thus, both polarization and directed migration of neutrophils are dependent on the expression of CD44 and its interaction with hyaluronan, which could modulate neutrophil migration into inflamed tissues.
在 Zigmond 小室中研究了 CD44 在小鼠中性粒细胞趋化作用中的重要性。野生型中性粒细胞比 CD44 - / - 中性粒细胞极化更快、更广泛，后者表现出缓慢的随机迁移和 RhoA 激活减少。CD44 + / - 中性粒细胞极化较慢，形成的定向极化细胞较少，并且比野生型细胞迁移更慢。抗 CD44 抗体降低了野生型中性粒细胞的极化并减少了定向迁移，但不影响迁移速度，这表明 CD44 通过不同途径介导趋化信号和迁移，而透明质酸基质显著降低了野生型细胞的速度和定向迁移。与巨噬细胞不同，中性粒细胞表面 CD44 的水平不受骨桥蛋白表达的影响，并且 CD44 与骨桥蛋白不共定位。在极化的中性粒细胞中，CD44 在尾足中富集，而皮质肌动蛋白在前缘占主导。因此，中性粒细胞的极化和定向迁移都依赖于 CD44 的表达及其与透明质酸的相互作用，这可能调节中性粒细胞向炎症组织的迁移。
