Mobilization of neutrophil sialidase activity desialylates the pulmonary vascular endothelial surface and increases resting neutrophil adhesion to and migration across the endothelium
Mobilization of neutrophil sialidase activity desialylates the pulmonary vascular endothelial surface and increases resting neutrophil adhesion to and migration across the endothelium
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DOI：
10.1093/glycob/cwh065
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发表时间：
2004-06-01
期刊：
影响因子：
4.3
通讯作者：
Goldblum, SE
中科院分区：
文献类型：
--
作者：
Sakarya, S;Rifat, S;Goldblum, SE
中性粒细胞（PMN）表面唾液酸的量影响其与其他细胞相互作用的能力。用各种刺激物激活PMN会使细胞内唾液酸酶动员到质膜，在质膜上它从细胞表面切割唾液酸。因为PMN的黏附增强、铺展、变形能力和运动性都与表面去唾液酸化相关，并且对PMN的渗出至关重要，所以我们在体外研究了唾液酸在PMN与肺血管内皮细胞（EC）单层的黏附和迁移中的作用。用神经氨酸酶处理PMN或EC都以剂量依赖的方式增加黏附和迁移。对PMN和EC都进行神经氨酸酶处理比单独处理PMN或EC更能增加PMN对EC的黏附。此外，用神经氨酸酶处理EC不会改变黏附分子的表面表达或白细胞介素 - 8（IL - 8）和白细胞介素 - 6（IL - 6）的释放。用交叉保护的抗神经氨酸酶抗体（抑制45.5%）或用伪底物竞争抑制（抑制41.2%）抑制内源性唾液酸酶会降低PMN对EC的黏附；可被抑制的唾液酸酶活性似乎与激活的PMN相关。最后，与激活的PMN预孵育的EC单层对随后添加的静息PMN变得高度黏附，并且这种高度黏附状态是通过内源性PMN唾液酸酶活性介导的。阻断抗E - 选择素、抗CD54和抗CD18抗体会降低PMN对肿瘤坏死因子激活的EC的黏附，但不会降低对PMN处理过的EC的黏附。这些数据表明去唾液酸化是一种新的机制，通过该机制PMN - EC的黏附可以在不依赖新蛋白质合成或黏附分子表达改变的情况下受到调节。激活的PMN通过内源性唾液酸酶活性使EC表面对未受刺激的PMN高度黏附的能力可能为PMN介导的宿主反应提供快速放大作用。
The amount of sialic acid on the surface of the neutrophil (PMN) influences its ability to interact with other cells. PMN activation with various stimuli mobilizes intracellular sialidase to the plasma membrane, where it cleaves sialic acid from cell surfaces. Because enhanced PMN adherence, spreading, deformability, and motility each are associated with surface desialylation and are critical to PMN diapedesis, we studied the role of sialic acid on PMN adhesion to and migration across pulmonary vascular endothelial cell (EC) monolayers in vitro. Neuraminidase treatment of either PMN or EC increased adhesion and migration in a dose-dependent manner. Neuraminidase treatment of both PMNs and ECs increased PMN adhesion to EC more than treatment of either PMNs or ECs alone. Moreover, neuraminidase treatment of ECs did not change surface expression of adhesion molecules or release of IL-8 and IL-6. Inhibition of endogenous sialidase by either cross-protective antineuraminidase antibodies (45.5% inhibition) or competitive inhibition with pseudo-substrate (41.2% inhibition) decreased PMN adhesion to ECs; the inhibitable sialidase activity appeared to be associated with activated PMNs. Finally, EC monolayers preincubated with activated PMNs became hyperadhesive for subsequently added resting PMNs, and this hyperadhesive state was mediated through endogenous PMN sialidase activity. Blocking anti-E-selectin, anti-CD54 and anti-CD18 antibodies decreased PMN adhesion to tumor necrosis factor-activated ECs but not to PMN-treated ECs. These data implicate desialylation as a novel mechanism through which PMN-EC adhesion can be regulated independent of de novo protein synthesis or altered adhesion molecule expression. The ability of activated PMNs, through endogenous sialidase activity, to render the EC surface hyperadherent for unstimulated PMNs may provide for rapid amplification of the PMN-mediated host response.