title: Pancreatic islets activate portal vein endothelial cells in vitro.
abstract: This study assessed the active role of the portal vein endothelium in the functional loss of pancreatic islet (PI) grafts, considered in the context of PI transplantation for treatment of type I diabetes mellitus. We hypothesized that PI engraftment may be jeopardized by portal vein endothelial cell-induced activation of host T cells. We designed an in vitro system using portal vein endothelial cells (PVEC) from Lewis (Lew) rats and PI from Brown-Norway (BN) and Lew rats. PI were co-cultured with Lew PVEC for three days. The PI were removed and trypsinized PVEC were divided into three groups: (A) PVEC not exposed to PI; (B) PVEC exposed to syngeneic PI; and (C) PVEC exposed to allogeneic PI. The groups were analyzed by flow cytometry for ICAM-1 and MHC Class I and Class II molecules. Functional assays of lymphocytes (ie, lymphocyte proliferation assay, 51Cr release assay, and cytokine release assay) were also performed. We observed MHC Class I and ICAM-1 upregulation on PVEC after PI contact. MHC Class II molecule was not upregulated on PVEC after PI exposure. IL-6 production was increased non-specifically following PI coculture with PVEC. TNF-a was increased only after allogeneic PI-PVEC coculture. PVEC exposed to either allogeneic or syngeneic PI could not stimulate naïve splenocyte proliferation or cytotoxicity. We conclude that PVEC allo-PI interaction results in increased ICAM-1 and MHC Class I expression on the PVEC. Neither lymphocyte proliferation nor cytotoxicity could be enhanced in response to enhanced MHC Class I and ICAM-1 expression, which was associated instead with non-specific inflammatory cytokine release.
authors.affiliation: Department of Pathology, Medical University of South Carolina, Charleston, South Carolina 29425, USA. fontainm@musc.edu
authors.forename: Magali J
authors.initials: MJ
authors.lastname: Fontaine
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Blanchard
authors.forename: Cristiana
authors.initials: C
authors.lastname: Rastellini
authors.forename: Velda
authors.initials: V
authors.lastname: Lazda
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
authors.forename: Raymond
authors.initials: R
authors.lastname: Pollak
mesh_terms: D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D011169:Portal Vein / Q000166:cytology / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1