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LUTHERAN BLOOD GROUP GLYCOPROTEINS AS NON-INTEGRIN RECEPTORS FOR LAMININ-10 IN THE HUMAN SMALL INTESTINE

I Teller, SF Parsons*, JF Beaulieu
Faculté de médecine, Département de biologie cellulaire, Sherbrooke, Quebec; *International Blood Group Reference Laboratory, Bristol Institute for Transfusion Sciences, Bristol, United Kingdom

Lutheran blood group glycoproteins have recently been recognized as receptors for the extracellular matrix proteins laminin-10 and laminin-11. The two membrane proteins known as LuGp and Lu(v13) also known as basal cell adhesion molecule (B-CAM) result from alternative splicing of the same gene and are members of the immunoglobulin superfamily. They are expressed on the surface of a subset of muscle and epithelial cells in diverse tissues. So far, the majority of research is done in context of blood group antigens and focused on their function in erythropoiesis and sickle cell disease. However, little is known for their expression and function in the intestinal epithelium, a tissue where laminin-10 was shown to induce differentiation. Aim of this study, was to examine the expression and function of LuGp and Lu(v13) in the developing and adult human small intestine. Indirect immunofluorescence revealed co-localization of LuGp with its ligand laminin-10 (alpha5-chain) in the basement membrane (BM) of the developing gut, while it was absent in the adult BM, but remained expressed in blood vessels. To investigate involvement of LuGps in epithelial differentiation, we determined transcript and protein levels in the Caco-2 cell line. These cells represent fetal colono- and enterocytes and spontaneously differentiate upon reaching confluence as determined by the differentiation markers sucrase-isomaltase and lactase-phlorizin hydrolase. LuGp expression on both transcript and protein levels are increasing with differentiation status of these cells. Lu(v13) transcript levels remained stable while the protein was in most cases too weak to detect by Western blot. Taken together, our data strongly suggest a crucial role of the LuGp receptor for the development of the human small intestine and differentiation status of enterocytes.

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