Brown K L, Maiti A, Johnson P
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
J Immunol. 2001 Nov 1;167(9):5367-74. doi: 10.4049/jimmunol.167.9.5367.
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 NaClO(3), an inhibitor of sulfation, prevented HA binding in a significant percentage of CD14(+) PBMC induced by TNF-alpha, LPS, IL-1beta, or IFN-gamma. Furthermore, stimulation with TNF-alpha or IFN-gamma in the presence of NaClO(3) 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 HA binding in T cells by PHA was not affected by NaClO(3), suggesting that activated T cells do not use sulfation as a mechanism to regulate HA 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.
抗原激活T细胞或用炎性细胞因子刺激单核细胞会诱导CD44与透明质酸（HA）结合，这一黏附事件与白细胞-白细胞、白细胞-内皮细胞及白细胞-基质细胞相互作用有关。我们之前已表明，肿瘤坏死因子-α（TNF-α）可诱导白血病细胞系中的CD44硫酸化，这与HA结合及CD44介导的黏附的诱导相关。在本研究中，我们证实TNF-α和干扰素-γ（IFN-γ）可诱导CD14(+)外周血单个核细胞（PBMC）中HA结合及CD44硫酸化，而在用TNF-α刺激的CD14(-) PBMC中未观察到诱导的HA结合或CD44硫酸化。用硫酸化抑制剂氯酸钠（NaClO₃）处理细胞，可在很大比例的由TNF-α、脂多糖（LPS）、白细胞介素-1β（IL-1β）或IFN-γ诱导的CD14(+) PBMC中阻止HA结合。此外，在存在NaClO₃的情况下用TNF-α或IFN-γ刺激可降低分离的CD44H与HA结合的能力，表明CD44H硫酸化对HA结合有直接作用。相反，PHA对T细胞中HA结合的短暂诱导不受NaClO₃影响，这表明活化的T细胞不将硫酸化用作调节HA结合的机制。总体而言，这些结果表明，CD44H的可诱导硫酸化是CD14(+)外周血单核细胞用于响应TNF-α和IFN-γ等炎性因子诱导HA结合的一种机制。
