title: Phosphatidylserine-dependent adhesion of T cells to endothelial cells.
abstract: Phosphatidylserine (PS) was exposed at the surface of human umbilical vein endothelial cells (HUVECs) and cultured cell lines by agonists that increase cytosolic Ca(2+), and factors governing the adhesion of T cells to the treated cells were investigated. Thrombin, ionophore A23187 and the Ca(2+)-ATPase inhibitor 2, 5-di-tert-butyl-1,4-benzohydroquinone each induced a PS-dependent adhesion of Jurkat T cells. A23187, which was the most effective agonist in releasing PS-bearing microvesicles, was the least effective in inducing the PS-dependent adhesion of Jurkat cells. Treatment of ECV304 and EA.hy926 cells with EGTA, followed by a return to normal medium, resulted in an influx of Ca(2+) and an increase in adhering Jurkat cells. Oxidised low-density lipoprotein induced a procoagulant response in cultured ECV304 cells and increased the number of adhering Jurkat cells, but adhesion was not inhibited by pretreating ECV304 cells with annexin V. PS was not significantly exposed on untreated Jurkat cells, as determined by flow cytometry with annexin V-FITC. However, after adhesion to thrombin-treated ECV304 cells for 10 min followed by detachment in 1 mM EDTA, there was a marked exposure of PS on the Jurkat cells. Binding of annexin V-FITC to the detached cells was inhibited by pretreating them with unlabelled annexin V. Contact with thrombin-treated ECV304 cells thus induced the exposure of PS on Jurkat cells and, as Jurkat cells were unable to adhere to thrombin-treated ECV304 cells in the presence of EGTA, the adhesion of the two cell types may involve a Ca(2+) bridge between PS on both cell surfaces. The number of T cells from normal, human peripheral blood that adhered to ECV304 cells was not increased by treating the latter with thrombin. However, findings made with several T cell lines were generally, but not completely, consistent with the possibility that adhesion to surface PS on endothelial cells may be a feature of T cells that express both CD4(+) and CD8(+) antigens. Possible implications for PS-dependent adhesion of T cells to endothelial cells in metastasis, and early in atherogenesis, are discussed.
authors.affiliation: Molecular Immunology Programme, The Brahabam Institute, Cambridge, UK.
authors.forename: J
authors.initials: J
authors.lastname: Qu
authors.forename: J
authors.initials: J
authors.lastname: Adam
authors.forename: D M
authors.initials: DM
authors.lastname: Bloxham
authors.forename: K R
authors.initials: KR
authors.lastname: Bruckdorfer
authors.forename: N G
authors.initials: NG
authors.lastname: Miller
authors.forename: N A
authors.initials: NA
authors.lastname: Parkinson
authors.forename: J A
authors.initials: JA
authors.lastname: Lucy
mesh_terms: D017304:Annexin A5 / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000031:analogs & derivatives / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D004533:Egtazic Acid; D004730:Endothelium, Vascular / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D010718:Phosphatidylserines / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D017304:Annexin A5; D007476:Ionophores; D008077:Lipoproteins, LDL; D010718:Phosphatidylserines; C099252:oxidized low density lipoprotein; D002083:Butylated Hydroxyanisole; D000001:Calcimycin; D004533:Egtazic Acid; C052101:2,5-di-tert-butyl-4-hydroxyanisole; D013917:Thrombin; D002118:Calcium