TAILIEUCHUNG - Báo cáo khoa học: Characterization of ICAM-4 binding to the I domains of the CD11a/CD18 and CD11b/CD18 leukocyte integrins

Intercellular adhesion molecule-4 (ICAM-4, LW blood group antigen), a member of the immunoglobulin super-familyexpressed on red cells, has been reported to bind to CD11a/CD18 and CD11b/CD18 leukocyte integrins. The location of the ICAM-4 binding sites on CD11a/CD18 and CD11b/CD18 are not known. CD11/CD18 integrin I domains have been found to act as major binding sites for physiological ligands and a negatively charged glutamic acid in ICAMs is considered important for binding. | Eur. J. Biochem. 270 1710-1723 2003 FEBS 2003 doi Characterization of ICAM-4 binding to the I domains of the CD11a CD18 and CD11b CD18 leukocyte integrins Eveliina Ihanus1 Liisa Uotila1 Anne Toivanen1 Michael Stefanidakis1 Pascal Bailly2 Jean-Pierre Cartron2 and Carl G. Gahmberg1 1 Department of Biosciences Division of Biochemistry University of Helsinki Finland 2INSERM U76 Institut National de Transfusion Sanguine Paris France Intercellular adhesion molecule-4 ICAM-4 LW blood group antigen a member of the immunoglobulin superfamily expesssed cm red cells has been reported to bind to CD11a CD18 and CD11b CD18 leukocyte integrins. The location of the ICAM-4 binding sites on CD11a CD18 and CD11b CD18 are not known. CD11 CD18 integrin I domains have been found to act as major binding sites for physiological ligands and a negatively charged glutamic acid in ICAMs is considered important for binding. ICAM-4 lacks such a residue which is replaced byan arginine. However we demonstrate here that ICAM-4 in red csIIs and transfected fibroblasts interacts specifically with die I domains of CD11a CD18 and CD11b CD18 integrins. The binding was inhibited byanti-I domain and anti-ICAM-4 antibodies and it was dependent on divalent cations. Inter estingly ICAM-4 negative red cells were still able to bind to the CD11b CD18 I domain but the binding of these cells to the CD11a CD18 I domain was clearly rndurdd. Using a solid phase assay we were able to show that isolated I domains directlyand specificallybind to purified recombinant ICAM-4 in a cation dependent manner. Competition experiments indicated that the binding sites in ICAM-4 for the CD11a and CD11b I domains are different. However the ICAM-4 binding region in both I domains seems to overlap with the regions recognized by hie nAWFl mid ICAM-2. Thus we have established that the I domains contain an ICAM-4 binding region in CD11a CD18 and CD11b CD18 leukocyte integrins. Keywords adhesion ICAM .

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