title: CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium.
abstract: To protect the body efficiently from infectious organisms, leukocytes circulate as nonadherent cells in the blood and lymph, and migrate as adherent cells into tissues. Circulating leukocytes in the blood have first to adhere to and then to cross the endothelial lining. CD31/PECAM-1 is an adhesion molecule expressed by vascular endothelial cells, platelets, monocytes, neutrophils, and naive T lymphocytes. It is a transmembrane glycoprotein of the immunoglobulin gene superfamily (IgSF), with six Ig-like homology units mediating leukocyte-endothelial interactions. The adhesive interactions mediated by CD31 are complex and include homophilic (CD31-CD31) or heterophilic (CD31-X) contacts. Soluble, recombinant forms of CD31 allowed us to study the heterophilic interactions in leukocyte adhesion assays. We show that the adhesion molecule alpha v beta 3 integrin is a ligand for CD31. The leukocytes revealed adhesion mediated by the second Ig-like domain of CD31, and this binding was inhibited by alpha v beta 3 integrin-specific antibodies. Moreover alpha v beta 3 was precipitated by recombinant CD31 from cell lysates. These data establish a third IgSF-integrin pair of adhesion molecules, CD31-alpha v beta 3 in addition to VCAM-1, MadCAM-1/alpha 4 integrins, and ICAM/beta 2 integrins, which are major components mediating leukocyte-endothelial adhesion. Identification of a further versatile adhesion pair broadens our current understanding of leukocyte-endothelial interactions and may provide the basis for the treatment of inflammatory disorders and metastasis formation.
authors.affiliation: Basel Institute for Immunology, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Piali
authors.forename: P
authors.initials: P
authors.lastname: Hammel
authors.forename: C
authors.initials: C
authors.lastname: Uherek
authors.forename: F
authors.initials: F
authors.lastname: Bachmann
authors.forename: R H
authors.initials: RH
authors.lastname: Gisler
authors.forename: D
authors.initials: D
authors.lastname: Dunon
authors.forename: B A
authors.initials: BA
authors.lastname: Imhof
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D001483:Base Sequence; D002412:Cations / Q000494:pharmacology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D008024:Ligands; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D008969:Molecular Sequence Data; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016024:Receptors, Cytoadhesin / Q000276:immunology / Q000378:metabolism*; D019030:Receptors, Vitronectin; D014407:Tumor Cells, Cultured
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D002412:Cations; D015815:Cell Adhesion Molecules; D016023:Integrins; D008024:Ligands; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin