Murphy Anne M, Sheils Orla M, McDonald George S A, Kelleher Dermot P
Department of Clinical medicine, Institute of Molecular medicine, Trinity Centre for Health Sciences, Saint James Hospital, Dublin 8, Ireland.
Mediators Inflamm. 2005 Feb 24;2005(1):23-30. doi: 10.1155/MI.2005.23.
Studies of tyrosine phosphorylation in the human duodenum have indicated that proliferating cells in the middle portion of the duodenal crypt were devoid of this feature, suggesting that tyrosine kinase activation is not a dominant factor in crypt cell proliferation, and that consequently tyrosine phosphatase activity may be a more critical factor in crypt cell development. We investigated the expression of the leukocyte common antigen-related receptor (LAR) family of tyrosine phosphatases. A flow cytometry system was used to examine cells from the surface, mid-portion, and lower part of the crypt. Individual cell populations were immunostained with anti-LAR antibodies using phycoerythrin-conjugated anti-CD3 to discriminate between epithelial cells (CD3-) and intraepithelial lymphocytes (CD3+). Epithelial cells expressed LAR throughout the crypt. Expression of LAR was maximal in the mid-portion of the crypt with lower expression at the top of the villi. Intraepithelial lymphocytes expressed low levels of LAR at the tips of the villi with stronger expression extending towards the base of the crypt. These findings were confirmed by immunohistochemistry on paraffin-fixed sections. Of note, peripheral blood lymphocytes expressed less LAR than IEL. These observations suggest the possibility that tyrosine phosphatase LAR may be of importance in the regulation of crypt cell proliferation. Moreover, as the extracellular domain of LAR has homology with adhesion molecules, the finding of this molecule on IEL could suggest a possible functional role in homing of this unique lymphocyte.
对人十二指肠酪氨酸磷酸化的研究表明,十二指肠隐窝中部的增殖细胞缺乏这一特征,这表明酪氨酸激酶激活不是隐窝细胞增殖的主导因素,因此酪氨酸磷酸酶活性可能是隐窝细胞发育中更关键的因素。我们研究了酪氨酸磷酸酶白细胞共同抗原相关受体(LAR)家族的表达。使用流式细胞术系统检测隐窝表面、中部和下部的细胞。使用藻红蛋白偶联的抗CD3抗体对单个细胞群体进行免疫染色,以区分上皮细胞(CD3-)和上皮内淋巴细胞(CD3+)。上皮细胞在整个隐窝中均表达LAR。LAR的表达在隐窝中部最高,在绒毛顶部表达较低。上皮内淋巴细胞在绒毛尖端表达低水平的LAR,向隐窝底部延伸时表达增强。这些发现通过石蜡包埋切片的免疫组织化学得到证实。值得注意的是,外周血淋巴细胞表达的LAR比上皮内淋巴细胞少。这些观察结果提示酪氨酸磷酸酶LAR可能在隐窝细胞增殖的调节中起重要作用。此外,由于LAR的细胞外结构域与黏附分子具有同源性,在IEL上发现该分子可能提示其在这种独特淋巴细胞归巢中的可能功能作用。