title: A peptide derived from the intercellular adhesion molecule-2 regulates the avidity of the leukocyte integrins CD11b/CD18 and CD11c/CD18.
abstract: beta 2 integrin (CD11a,b,c/CD18)-mediated cell adhesion is required for many leukocyte functions. Under normal circumstances, the integrins are nonadhesive, and become adhesive for their cell surface ligands, the intercellular adhesion molecules (ICAMs), or soluble ligands such as fibrinogen and iC3b, when leukocytes are activated. Recently, we defined a peptide derived from ICAM-2, which specifically binds to purified CD11a/CD18. Furthermore, this peptide strongly induces T cell aggregation mainly mediated by CD11a/CD18-ICAM-1 interaction, and natural killer cell cytotoxicity. In the present study, we show that the same ICAM-2 peptide also avidly binds to purified CD11b/CD18, but not to CD11c/CD18. This binding can be blocked by the CD11b antibody OKM10. The peptide strongly stimulates CD11b/CD18-ICAM-1-mediated cell aggregations of the monocytic cell lines THP-1 and U937. The aggregations are energy and divalent cation-dependent. The ICAM-2 peptide also induces CD11b/CD18 and CD11c/CD18-mediated binding of THP-1 cells to fibrinogen and iC3b coated on plastic. These findings indicate that in addition to induction of CD11a/CD18-mediated cell adhesion, the ICAM-2 peptide may also serve as a "trigger" for high avidity ligand binding of other beta 2 integrins.
authors.affiliation: Department of Biochemistry, University of Helsinki, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Xie
authors.forename: C
authors.initials: C
authors.lastname: Kantor
authors.forename: V
authors.initials: V
authors.lastname: Koistinen
authors.forename: D C
authors.initials: DC
authors.lastname: Altieri
authors.forename: P
authors.initials: P
authors.lastname: Nortamo
authors.forename: C G
authors.initials: CG
authors.lastname: Gahmberg
mesh_terms: D008841:Actin Cytoskeleton; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism; D002413:Cations, Divalent; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D003179:Complement C3b / Q000378:metabolism; D004734:Energy Metabolism; D005340:Fibrinogen / Q000378:metabolism; D016167:Integrin alphaXbeta2 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D018821:CD18 Antigens; D002413:Cations, Divalent; D016167:Integrin alphaXbeta2; D016177:Macrophage-1 Antigen; D016028:Receptors, Leukocyte-Adhesion; D018799:Intercellular Adhesion Molecule-1; D003179:Complement C3b; D005340:Fibrinogen