Koh Adeline, da Silva Andre Paes Batista, Bansal Anil K, Bansal Manju, Sun Chunxiang, Lee Hyejin, Glogauer Michael, Sodek Jaro, Zohar Ron
CIHR Group in Matrix Dynamics, Faculty of Dentistry, Department of Biochemistry, University of Toronto, Toronto, ONT, Canada.
Immunology. 2007 Dec;122(4):466-75. doi: 10.1111/j.1365-2567.2007.02682.x. Epub 2007 Aug 3.
Osteopontin (OPN) is important for the function of fibroblasts, macrophages and lymphocytes during inflammation and wound healing. In recent studies of experimental colitis we demonstrated exacerbated tissue destruction in OPN-null mice, associated with reduced tumour necrosis factor-alpha expression and increased myeloperoxidase activity. The objective of this investigation therefore was to determine the importance of OPN expression in neutrophil function. Although, in contrast to macrophages, neutrophils expressed low levels of OPN with little or no association with the CD44 receptor, intraperitoneal recruitment of neutrophils in OPN-null mice was impaired in response to sodium periodate. The importance of exogenous OPN for neutrophil recruitment was demonstrated by a robust increase in peritoneal infiltration of PMNs in response to injections of native or recombinant OPN. In vitro, OPN(-/-) neutrophils exhibited reduced chemokinesis and chemotaxis towards N-formyl methionyl leucyl phenylalanine (fMLP), reflecting a reduction in migration speed and polarization. Exogenous OPN, which was chemotactic for the neutrophils, rescued the defects in polarization and migration speed of the OPN(-/-) neutrophils. In contrast, the defensive and cytocidal activities of OPN(-/-) neutrophils, measured by assays for phagocytosis, generation of reactive oxygen species, cytokine production and matrix metalloproteinase-9, were not impaired. These studies demonstrate that, while exogenous OPN may be important for the recruitment and migration of neutrophils, expression of OPN by neutrophils is not required for their destructive capabilities.
骨桥蛋白（OPN）在炎症和伤口愈合过程中对成纤维细胞、巨噬细胞和淋巴细胞的功能很重要。在最近关于实验性结肠炎的研究中，我们证明了OPN基因敲除小鼠的组织破坏加剧，这与肿瘤坏死因子-α表达降低和髓过氧化物酶活性增加有关。因此，本研究的目的是确定OPN表达在中性粒细胞功能中的重要性。虽然与巨噬细胞不同，中性粒细胞表达的OPN水平较低，与CD44受体几乎没有关联，但在高碘酸钠刺激下，OPN基因敲除小鼠中性粒细胞的腹腔募集受损。通过注射天然或重组OPN后，多形核白细胞（PMN）腹腔浸润显著增加，证明了外源性OPN对中性粒细胞募集的重要性。在体外，OPN基因敲除的中性粒细胞对N-甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）的趋化运动和趋化性降低，反映出迁移速度和极化的降低。对中性粒细胞具有趋化作用的外源性OPN挽救了OPN基因敲除中性粒细胞在极化和迁移速度方面的缺陷。相比之下，通过吞噬作用、活性氧生成、细胞因子产生和基质金属蛋白酶-9测定来衡量的OPN基因敲除中性粒细胞的防御和杀细胞活性并未受损。这些研究表明，虽然外源性OPN可能对中性粒细胞的募集和迁移很重要，但中性粒细胞表达OPN对其破坏能力并非必需。
