title: Integrin alpha E(CD103)beta 7 mediates adhesion to intestinal microvascular endothelial cell lines via an E-cadherin-independent interaction.
abstract: Integrins are important for T cell interactions with endothelial cells. Because the integrin alpha(E)beta(7) is expressed on some circulating gut-homing T cells and as T cell numbers are reduced in the intestinal lamina propria of alpha(E)-deficient mice, we evaluated whether alpha(E)beta(7) mediates binding to intestinal endothelial cells. We found that anti-alpha(E)beta(7) mAbs partially blocked the binding of cultured intraepithelial T cells to human intestinal microvascular endothelial cells (HIMEC). Furthermore, alpha(E)beta(7)-transfected K562 cells bound more efficiently than vector-transfected K562 cells to HIMEC. Finally, HIMEC bound directly to an alpha(E)beta(7)-Fc fusion protein. These interactions were partially blocked by anti-alpha(E)beta(7) mAbs, and endothelial cell binding to the alpha(E)beta(7)-Fc was dependent upon the metal ion-dependent adhesion site within the alpha(E) A domain. Of note, the HIMEC lacked expression of E-cadherin, the only known alpha(E)beta(7) counterreceptor as assessed by functional studies, flow cytometry, and RT-PCR. Thus, HIMEC/alpha(E)beta(7) binding was independent of E-cadherin. In addition, this interaction appeared to be tissue selective, as HIMEC bound to the alpha(E)beta(7)-Fc, whereas microvascular endothelial cells from the skin did not. Finally, there was evidence for an alpha(E)beta(7) ligand on intestinal endothelial cells in vivo, as alpha(E)beta(7) expression enhanced lymphocyte binding around vessels in the lamina propria in tissue sections. Thus, we have defined a novel interaction for alpha(E)beta(7) at a nonepithelial location. These studies suggest a role for alpha(E)beta(7) in interactions with the intestinal endothelium that may have implications for intestinal T cell homing or functional responses.
authors.affiliation: The Lymphocyte Biology Section, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: U G
authors.initials: UG
authors.lastname: Strauch
authors.forename: R C
authors.initials: RC
authors.lastname: Mueller
authors.forename: X Y
authors.initials: XY
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Cernadas
authors.forename: J M
authors.initials: JM
authors.lastname: Higgins
authors.forename: D G
authors.initials: DG
authors.lastname: Binion
authors.forename: C M
authors.initials: CM
authors.lastname: Parker
mesh_terms: D019138:Antibodies, Blocking / Q000378:metabolism / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism; D039001:Integrin alpha Chains; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020014:K562 Cells; D008670:Metals / Q000378:metabolism; D008833:Microcirculation / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000098:blood supply / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012995:Solubility; D014407:Tumor Cells, Cultured
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015820:Cadherins; D007141:Immunoglobulin Fc Fragments; D039001:Integrin alpha Chains; D016023:Integrins; D008670:Metals; D011993:Recombinant Fusion Proteins; C091367:alpha E integrins; C070709:integrin alphaEbeta7