title: Alterations in human endothelial cell morphology, proliferation and function by a macrophage-derived factor.
abstract: Changes in endothelial cell (EC) morphology occur at sites of physiological lymphocyte traffic and in areas of chronic inflammation. Previous studies have shown that EC shape changes also occur in vitro following exposure of EC monolayers to peripheral blood mononuclear cell (PBMC)-derived conditioned media (CM). In the present study, quantitative image analysis is used to define the cell of origin of the elongating factor(s), to examine changes in EC proliferation and function accompanying PBMC-induced human EC elongation and to identify the active PBMC-derived products responsible for this elongation. By separating mononuclear cells into subpopulations (macrophages, B cells and T cells) and adding conditioned media derived from these subpopulations to cultured ECs, the macrophage (M phi) is shown to be the primary cell of origin of the elongating factor(s). Furthermore, EC elongation is accompanied by both a dose-dependent decrease in cellular proliferation and an increase in prostacyclin production. These findings suggest that PBMC-induced changes in EC morphology may be associated with a shift from a proliferative state to a more secretory phase of the EC cycle. Finally, using recombinant factors it is shown that TNF alpha acting in combination with IL-1 may be the active PBMC-derived products which contribute to EC elongation.
authors.affiliation: Department of Rheumatology, St. Vincent's Hospital, Dublin, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Heffernan
authors.forename: A
authors.initials: A
authors.lastname: Chance
authors.forename: E V
authors.initials: EV
authors.lastname: Hess
authors.forename: R F
authors.initials: RF
authors.lastname: Highsmith
authors.forename: O
authors.initials: O
authors.lastname: FitzGerald
mesh_terms: D002455:Cell Division; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*
chemical_list: D006133:Growth Substances