Phorbol ester-stimulated T lymphocytes show enhanced adhesion to human endothelial cell monolayers.
Phorbol esters have been used to study changes in the adhesiveness of T cells to endothelial cells (EC) after activation. The phorbol esters 12-O-tetra-decanoylphorbol-13-acetate (TPA) and 4-beta-phorbol-12,13-dibutyrate (P(Bu)2), but not the biologically inert 4-alpha-phorbol-12,13-didecanoate, strongly increased the binding of 51Cr-labeled T cells to human umbilical vein EC monolayers in microtiter wells. Binding to fibroblasts and gelatin-coated plastic was also increased, but to a lesser extent. Increased binding was observed at 0.3 ng/ml, with maximal enhancement at 33 to 100 ng/ml. Enhancement occurred within 1 min, with maximal increase after 15 min. Preincubation studies with P(Bu)2 showed that binding enhancement was entirely attributable to an effect on T cells, with no action on EC. Additive binding enhancement was seen when phorbol esters and agents that alter adhesion by acting on EC (LPS, IL 1, or IFN-gamma) were used together. The increase in T cell adhesion to EC after T cell activation may contribute to the selective emigration of activated T cells from the blood into developing inflammatory lesions. The rapid increase in binding suggests that this may be an important mechanism for immediate localization of circulating T cells, particularly sensitized T cells, in the cellular immune response, perhaps involving the activation of these cells at the endothelial blood-tissue interface.
D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004727:Endothelium / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology; D005780:Gelatin; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014471:Umbilical Veins
D007375:Interleukin-1; D008070:Lipopolysaccharides; D010703:Phorbol Esters; D010704:Phorbols; C008876:phorbol-12,13-didecanoate; D015240:Phorbol 12,13-Dibutyrate; D007371:Interferon-gamma; D005780:Gelatin; D013755:Tetradecanoylphorbol Acetate