PMID: 20127050Feb 4, 2010Paper

The alpha integrin cytoplasmic motif KXGFFKR is essential for integrin-mediated leukocyte adhesion

International Journal of Molecular Medicine
Masayoshi Ohkuro, Ieharu Hishinuma

Abstract

During the development of autoimmune and inflammatory diseases, infiltration by multiple leukocyte types is commonly observed at the site of inflammation. These cells are chemotactically recruited via activated integrins expressed on their cell surfaces. However, the detailed mechanism of integrin activation has not been fully elucidated. A specific and highly conserved cytoplasmic amino acid sequence, lysine-x-glycine-phenylalanine-phenylalanine-lysine-arginine (KXGFFKR), is located in the immediate vicinity of the membrane-spanning domain of all alpha integrins. In this study, we investigated the role of the KXGFFKR motif in the adhesion of leukocytes to human umbilical-vein endothelial cells (HUVEC). Pre-treatment of human neutrophils with a membrane-permeable peptide-linked KVGFFKR decreased cell adhesion to HUVEC induced by a complement activation product, C5a and formyl-methionine-leucine-phenylalanine. Similar inhibitory efficacies of this peptide were observed in T cell adhesion. Our data therefore demonstrate that a highly conserved sequence in the alpha integrins, KXGFFKR, is pharmacologically essential for integrin activation during leukocyte adhesion by both neutrophils and T cells.

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