SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum
SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum
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DOI：
10.1074/jbc.m506703200
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发表时间：
2006-07-21
影响因子：
4.8
通讯作者：
Kimata, Koji
中科院分区：
文献类型：
--
作者：
Zhuo, Lisheng;Kanamori, Akiko;Kimata, Koji
cd44 -透明质酸（HA）相互作用参与多种生理和病理过程。相互作用亲和度的调控在CD44上得到了很好的研究，但在HA上却很少。我们发现了一种独特的HA共价修饰蛋白，SHAP，对应于血液中循环的α -胰蛋白酶抑制剂家族分子的重链。SHAP的形成（.）HA复合物通常与炎症有关，这是一个众所周知的涉及CD44-HA相互作用的过程。因此，我们研究了SHAP对CD44-HA相互作用介导的淋巴细胞粘附的影响。在静态和流动条件下，hu78细胞（cd44阳性）和转染cd44的Jurkat细胞（最初是cd44阴性）优先粘附在固定的SHAP上（）。HA复合体比HA。这种增强的粘附完全是由CD44-HA相互作用介导的，因为它被HA抑制，而不是I α I，并且通过抗cd44抗体预处理细胞完全消除。SHAP似乎通过增加HA对CD44的亲和力和改变它们在细胞表面的分布来增强这种相互作用。大量的SHAP（。）类风湿关节炎患者增生性滑膜中HA复合物的积累。浸润到滑膜的白细胞表面的HA、SHAP和CD44均呈强阳性，提示SHAP在滑膜的发病机制中具有增强黏附的作用。
CD44-hyaluronan (HA) interaction is involved in diverse physiological and pathological processes. Regulation of interacting avidity is well studied on CD44 but rarely on HA. We discovered a unique covalent modification of HA with a protein, SHAP, that corresponds to the heavy chains of inter-alpha-trypsin inhibitor family molecules circulating in blood. Formation of the SHAP(.)HA complex is often associated with inflammation, a well known process involving the CD44-HA interaction. We therefore examined the effect of SHAP on the CD44-HA interaction-mediated lymphocyte adhesion. Under both static and flowing conditions, Hut78 cells (CD44-positive) and CD44-transfected Jurkat cells (originally CD44-negative) adhered preferentially to the immobilized SHAP(.)HA complex than to HA. The enhanced adhesion is exclusively mediated by the CD44-HA interaction, because it was inhibited by HA, but not I alpha I, and was completely abolished by pretreating the cells with anti-CD44 antibodies. SHAP appears to potentiate the interaction by increasing the avidity of HA to CD44 and altering their distribution on cell surfaces. Large amounts of the SHAP(.)HA complex accumulate in the hyperplastic synovium of rheumatoid arthritis patients. Leukocytes infiltrated to the synovium were strongly positive for HA, SHAP, and CD44 on their surfaces, suggesting a role for the adhesion-enhancing effect of SHAP in pathogenesis.