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Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4

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dc.contributor.author Ihanus, E en
dc.contributor.author Uotila, LM en
dc.contributor.author Toivanen, A en
dc.contributor.author Varis, M en
dc.contributor.author Gahmberg, CG en
dc.date.accessioned 2006-11-28T07:31:22Z en
dc.date.accessioned 2009-06-17T13:58:37Z
dc.date.available 2006-11-28T07:31:22Z en
dc.date.available 2009-06-17T13:58:37Z
dc.date.issued 2007 en
dc.identifier.citation Blood. 2007. 109(2): 802-810. en
dc.identifier.issn 0006-4971 en
dc.identifier.uri http://dx.doi.org/10.1182/blood-2006-04-014878 en
dc.identifier.uri http://hdl.handle.net/1975/714
dc.description.abstract Intercellular adhesion molecule-4 (ICAM-4) is a unique member of the ICAM family due to its specific expression on erythroid cells and ability to interact with several types of integrins expressed on blood and endothelial cells. The first reported receptors for ICAM-4 were CD11a/CD18 and CD11b/CD18. In contrast to these two, the cellular ligands and the functional role of the third beta2-integrin, CD11c/CD18, have not been well defined. Here we show that ICAM-4 functions as a ligand for the monocyte/macrophage specific CD11c/CD18. Deletion of the individual immunoglobulin domains of ICAM-4 demonstrated that both its domains contain binding sites for CD11c/CD18. Analysis of a panel of ICAM-4 point mutants identified residues that affected binding to the integrin. By molecular modeling the important residues were predicted to cluster in two distinct but spatially close regions of the first domain with an extension to the second domain spatially distant from the other residues. We also identified two peptides derived from sequences of ICAM-4 that are capable of modulating the binding to CD11c/CD18. CD11c/CD18 is expressed on macrophages in spleen and bone marrow. Inhibition of erythrophagocytosis by anti-ICAM-4 and anti-integrin antibodies suggests a role for these interactions in removal of senescent red cells. en
dc.format.extent 24064 bytes en
dc.format.mimetype application/msword en
dc.language.iso en en
dc.publisher American Society of Hematology en
dc.title Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4 en
dc.type Article en
dc.identifier.laitoskoodi B57118 fi
dc.creator.corporateName Biokemia (Bio- ja ympäristötieteiden laitos) fi
dc.creator.corporateName Biochemistry (Department of Biological and Environmental Sciences) en
dc.creator.corporateName Biokemi (Institutionen för bio- och miljövetenskaper) sv

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