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

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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 α 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 α integrins, KXGFFKR, is pharmacologically essential for integrin activation during leukocyte adhesion by both neutrophils and T cells.
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Document Type: Research Article

Affiliations: Tsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan., Email: [email protected]

Publication date: January 1, 2010

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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