title: Heart EC respond heterogeneous on cytokine stimulation in ICAM-1 and VCAM-1, but not in MHC expression. A study with 3 rat heart endothelial cell (RHEC) lines.
abstract: Cytokine-induced expression of ICAM-1, VCAM-1, and MHC class I and II was studied at different time points in microvascular endothelial cells (EC) of heart origin, using three different rat endothelial cell (RHEC) lines that were stimulated with TNFalpha and/or IFNgamma. Each of the three RHEC lines responded to TNFalpha as well as to IFNgamma; stimulation with combined cytokines led to increased or even synergistic effects. TNFalpha was most potent in inducing ICAM-1 and VCAM-1, whereas MHC class II was most effectively induced by IFNgamma. The 3 RHEC lines responded similarly regarding induction of MHC class II and upregulation of constitutively expressed MHC class I on the cells. However, the RHEC lines showed remarkable differences with respect to ICAM-1 and VCAM-1 induction, with each line having a unique expression profile. In RHEC-3, both ICAM-1 and VCAM-1 were well inducible, whereas in RHEC-10, no ICAM-1 and only some VCAM-1 could be induced. RHEC-11 showed minimal induction of ICAM-1, but strong induction of VCAM-1. For P-selectin induction, no such differences were found between the RHEC lines. These heterogeneous effects of cytokine stimulation could neither be explained by differences in mobilization of calcium nor by ultra-structural differences between the lines. Stimulation of the RHEC lines for ICAM-1 and VCAM-1 or MHC class II molecule induction resulted in expressing and non-expressing EC. Experiments with selected and subsequently cultured expressing and non-expressing cell populations for either ICAM-1, VCAM-1 or MHC class II, indicated that this selective induction most likely results from intrinsic regulation mechanisms in the cell cultures, and not from the presence of particular EC subpopulations within the lines. We conclude that microvascular heart endothelial cells, as represented by the 3 RHEC lines, demonstrate a selective heterogeneity in expression of ICAM-1 and VCAM-1, but not of MHC class I and II, upon cytokine stimulation. The consequences of this heterogeneity for leukocyte-endothelial cell interactions in heart inflammation and immune reactivity is discussed.
authors.affiliation: Department of Immunology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: Derhaag
authors.forename: A M
authors.initials: AM
authors.lastname: Duijvestijn
authors.forename: P J
authors.initials: PJ
authors.lastname: Van Breda Vriesman
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D004699:Endocardium / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006649:Histocompatibility Antigens / Q000096:biosynthesis* / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology*; D019007:P-Selectin / Q000096:biosynthesis / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D006649:Histocompatibility Antigens; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C038353:histocompatibility antigens RT, rat; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate