Role of sulfation in CD44-mediated hyaluronan binding induced by inflammatory mediators in human CD14+ peripheral blood monocytes
Role of sulfation in CD44-mediated hyaluronan binding induced by inflammatory mediators in human CD14+ peripheral blood monocytes
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DOI：
10.4049/jimmunol.167.9.5367
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发表时间：
2001-11-01
影响因子：
4.4
通讯作者：
Johnson, P
中科院分区：
文献类型：
--
作者：
Brown, KL;Maiti, A;Johnson, P
Ag激活T细胞或炎症细胞因子刺激单核细胞可诱导CD44与透明质酸（HA）结合，这是一种涉及白细胞-白细胞、白细胞-内皮细胞和白细胞-基质细胞相互作用的粘附事件。我们之前已经证明tnf - α在白血病细胞系中诱导CD44硫酸化，这与诱导HA结合和CD44介导的粘附相关。在这项研究中，我们证实了tnf - α和ifn - γ诱导CD14(+) PBMC中HA结合和CD44硫酸化，而tnf - α刺激的CD14(-) PBMC中未观察到诱导HA结合或CD44硫酸化。用NaClO3（一种磺化抑制剂）处理细胞，可显著阻止tnf - α、LPS、IL-1 β或ifn - γ诱导的CD14(+) PBMC中HA的结合。此外，在NaClO3存在的情况下，tnf - α或ifn - γ刺激降低了分离的CD44H结合HA的能力，这表明CD44H磺化对HA结合有直接影响。相比之下，PHA在T细胞中诱导IIA的瞬时结合不受NaClO3的影响，这表明活化的T细胞不使用硫酸化作为调节IIA结合的机制。总的来说，这些结果表明CD44H的诱导硫酸化是CD14（+）外周血单核细胞在对炎症因子如tnf - α和ifn - γ的反应中诱导HA结合的一种机制。
Activation of T cells by Ag or stimulation of monocytes with inflammatory cytokines induces CD44 to bind to hyaluronan (HA), an adhesion event implicated in leukocyte-leukocyte, leukocyte-endothelial cell, and leukocyte-stromal cell interactions. We have previously shown that TNF-alpha induces CD44 sulfation in a leukemic cell line, which correlated with the induction of HA binding and CD44-mediated adhesion. In this study, we establish that TNF-alpha and IFN-gamma induce HA binding and the sulfation of CD44 in CD14(+) PBMC, whereas no induced HA binding or CD44 sulfation was observed in CD14(-) PBMC stimulated with TNF-alpha. Treatment of cells with NaClO3, an inhibitor of sulfation, prevented HA binding in a significant percentage of CD14(+) PBMC induced by TNF-alpha, LPS, IL-1 beta, or IFN-gamma. Furthermore, stimulation with TNF-alpha or IFN-gamma in the presence of NaClO3 reduced the ability of isolated CD44H to bind HA, demonstrating a direct effect of CD44H sulfation on HA binding. In contrast, the transient induction of IIA binding in T cells by PHA was not affected by NaClO3, suggesting that activated T cells do not use sulfation as a mechanism to regulate IIA binding. Overall, these results demonstrate that inducible sulfation of CD44H is one mechanism used by CD14(+) peripheral blood monocytes to induce HA binding in response to inflammatory agents such as TNF-alpha and IFN-gamma.