title: Expression of functionally active alpha 4 beta 1 integrin by thymic epithelial cells.
abstract: We have investigated the expression and function of the VLA-4 heterodimer alpha 4 beta 1, a member of the beta 1 integrin subfamily, on human thymic epithelial cells (TEC) derived from cortical epithelium. The expression of the alpha 4 integrin chain was studied in four different cloned TEC lines derived from either fetal or post-natal human thymus by both flow cytometry and immunoprecipitation techniques with anti-alpha 4 MoAbs. All different cell lines assayed expressed significant levels of alpha 4, as revealed by their reactivity with MoAbs specific for distinct alpha 4 epitopes. The alpha 4 subunit expressed by TEC was associated to beta 1 but not to beta 1 chain, and displayed the characteristic 80/ 70 kD pattern of proteolytic cleavage. The VLA-4 integrin in these cells was constitutively active in terms of adhesiveness to both fibronectin and vascular cell adhesion molecule-1 (VCAM-1). In addition, this heterodimer localized to punctate regions of the cell in the area of contact with the substratum, named point contacts assessed by staining with the anti-beta 1 activation epitope 15/7 MoAb. According to the cortical origin of the TEC lines expressing VLA-4, human thymus sections stained with different anti-alpha 4 antibodies revealed the presence of cortical, and in smaller numbers medullary epithelial cells bearing alpha 4 integrin. The expression of alpha 4 in the thymus was also found in both adult and fetal rats, in which epithelial cells were also specifically stained. Altogether, our data show that VLA-4 is an additional component of the integrin repertoire of TEC, and suggest that it could have an important role in thymus epithelial cell-thymocyte interactions.
authors.affiliation: Servicio de Immunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Nieto
authors.forename: M
authors.initials: M
authors.lastname: Gómez
authors.forename: P
authors.initials: P
authors.lastname: Sánchez-Mateos
authors.forename: E
authors.initials: E
authors.lastname: Fernández
authors.forename: M
authors.initials: M
authors.lastname: Marazuela
authors.forename: R
authors.initials: R
authors.lastname: Sacedón
authors.forename: A
authors.initials: A
authors.lastname: Varas
authors.forename: R
authors.initials: R
authors.lastname: González-Amaro
authors.forename: A G
authors.initials: AG
authors.lastname: Zapata
authors.forename: M L
authors.initials: ML
authors.lastname: Toribio
authors.forename: F
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D000818:Animals; D002460:Cell Line; D004848:Epithelium / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007223:Infant; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology*; D013194:Staining and Labeling; D013950:Thymus Gland / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
chemical_list: D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing