CD44/AND HYALURONAN IN SKIN INFLAMMATION AND AUTOIMMUNITY--ADHESION PATHWAY

1.使用皮肤接触超敏反应模型（DTH），检查 淋巴细胞上的CD 44调节与HA表达变化的关系 在该部位的血管内皮上;确定 CD 44/HA相互作用对炎症浸润和反应的影响。 2.同时，确定CD 44/HA相互作用对 银屑病小鼠模型的炎症过程。 3.检查另外的细胞因子在体内和体外对 HA表达的改变。 背景和意义。很明显，特殊性和监管 白细胞粘附内皮细胞的结果是， 粘附受体的类型可以以顺序和协调的方式起作用。 主要针对中性粒细胞建立的粘附的主要步骤包括 白细胞与血管壁接触的主要事件， 然后通过重复的瞬时相互作用/释放， “滚动”。这是其次是一个二次坚定的粘附力的滚动 细胞和随后的轮回（，2）。主要粘合剂已 一般归因于他selectin家庭（1，3 -6），而次要（坚定） 粘附是由于异二聚体β 2整联蛋白（1，6）。因为机制 淋巴细胞运输的复杂性， 不同的子集，有时是组织特异性的，归巢行为，它会 如果其他配体对参与淋巴细胞 与内皮细胞的相互作用。我们最近把一部小说 淋巴样细胞和贴壁培养的细胞之间的初级（滚动）相互作用 内皮细胞（EC），其不是选择素或整合素介导的（7）。我们 研究表明，这种新的粘附途径的结果， 蛋白聚糖核心/软骨连接蛋白家族之间的相互作用 CD 44及其主要配体透明质酸（HA）。

1. Using a skin contact hypersensitivity model (DTH), examine the regulation of CD44 on lymphocytes in relation to changes in HA expression on vascular endothelium at the site; determine the contribution of the CD44/HA interaction tot he inflammatory infiltrate and response. 2. In parallel, determine the contribution of the CD44/HA interaction to the inflammatory process in a mouse model of psoriasis. 3. Examine the effect of additional cytokines in vivo and in vitro for alteration of HA expression. Background & Significance. It is clear that the specificity and regulation of adhesion of leukocytes to endothelium results from the fact that various types of adhesion receptors can act in sequential and coordinate fashion. The major steps of adhesion, established primarily for neutrophils, include a primary event during which leukocytes are engaged by the vessel wall and then retarded by a repeated transient interaction/release, called "rolling". This is followed by a secondary firm adhesion of the rolling cells and subsequent transmigration (,2). Primary adhesion has been generally attributed tot he selectin family (1,3-6), while secondary (firm) adhesion is due to heterodimeric beta2 integrins (1,6). Because mechanisms of lymphocyte trafficking must accommodate the complexities of myriad subsets of distinct, sometimes tissue-specific, homing behaviors, it would not be surprising if other ligand pairs participated in lymphocyte interactions with endothelium. We have recently characterize a novel primary (rolling) interaction between lymphoid cells and adherent cultured endothelial cells (EC) which is not selectin or integrin mediated (7). Our studies indicate that this novel adhesion pathway results from the interactions between the proteoglycan core/cartilage link protein family member, CD44, and its principal ligand hyaluronate (HA).