title: Monocytes initiate a cycle of leukocyte recruitment when cocultured with endothelial cells.
abstract: During the development of atherosclerotic plaque, monocytes and T-lymphocytes are recruited to the arterial intima by endothelial cells (EC) lining the vessel. This process is associated with chronic arterial inflammation and requires the activation-dependent expression of adhesion receptors and chemokines on EC. Here we show that monocytes can activate cocultured EC so that they support the adhesion, activation and transmigration of a secondary bolus of flowing peripheral blood monocytes or lymphocytes. The number of adherent leukocytes and their behaviour was comparable to that seen on EC activated with tumour necrosis factor-alpha (TNF-alpha). Depending upon the duration of endothelial cell/monocyte coculture different patterns of adhesion receptors were utilised by leukocytes. After 4 h coculture, antibodies against E-selectin, P-selectin and vascular cell adhesion molecule-1 (VCAM-1) reduced mononuclear leukocyte adhesion. After 24 h coculture, antibodies against E-selectin and VCAM-1 but not P-selectin were effective. Immunofluorescence analysis confirmed that monocyte coculture induced endothelial expression of E-selectin and VCAM-1, while P-selectin was at the limit of detection. We conclude that EC stimulated by monocytes can support the adhesion of flowing mononuclear leukocytes. We hypothesise that this mode of EC activation and leukocyte recruitment could initiate a self-perpetuating cycle of inflammation that could be relevant to atherogenesis and other chronic inflammatory disease states.
authors.affiliation: The Department of Physiology, Cardiovascular Rheology Group, The Medical School, The University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Tsouknos
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Nash
authors.forename: G Ed
authors.initials: GE
authors.lastname: Rainger
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001711:Biotransformation / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D039041:Integrin alpha4beta1 / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D019007:P-Selectin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D012016:Reference Values; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D019040:E-Selectin; D039041:Integrin alpha4beta1; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1