title: Secretion of a novel T-lymphocyte cytokine possessing both chemotactic and growth factor activity by serotonin-stimulated human aortic endothelial cells.
abstract: The development of an extralymphatic T-lymphocyte focus of inflammation requires chemoattractant-induced cell migration and growth factor-induced cell proliferation. In a previous study, we identified a novel 13- to 15-kDa T-lymphocyte-specific chemotactic cytokine, endothelial cell-derived lymphocyte chemoattractant activity (ED-LCA), secreted by serotonin-stimulated human aortic endothelial cells. Based on its physicochemical and functional characteristics and antibody inhibition studies, ED-LCA is distinct from previously identified endothelial cell-derived IL-1, IL-6, and IL-8. Because of the association between T-lymphocyte chemotactic and growth factor activity, in the current study, we investigated the effect of ED-LCA on T cell growth by assessing its capacity to induce markers of the passage of T cells from the resting (G0) state into the G1 phase of the cell cycle, such as receptors for IL-2 (IL-2R) and transferrin (TFR), and class II major histocompatibility complex antigens (HLA-DR). Incubation of G0 freshly isolated human T lymphocytes for 48 h with chromatographically resolved, partially purified ED-LCA resulted in a threefold increase in expression of IL-2R, a threefold increase in TFR, and a twofold increase in HLA-DR. Double antibody labeling demonstrated that IL-2R was induced in both CD4+ and CD8+ T cell subsets. Although incubation of human T cells with ED-LCA alone did not induce DNA synthesis, addition of exogenous IL-2 to T cells pulsed with ED-LCA for 24 h caused an increase in DNA synthesis with a stimulation index of 3.5. By up-regulating functional cell surface receptors for IL-2 on T lymphocytes and priming them to respond to exogenous IL-2, ED-LCA is a competence growth factor. By virtue of its effect on T cells, as a chemotactic and competence factor, this endothelial cell-derived mitoattractant could participate with other T-cell growth factors like IL-2 in the generation of an extralymphatic T-lymphocyte inflammatory response.
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Massachusetts 02118.
authors.forename: M F
authors.initials: MF
authors.lastname: Katz
authors.forename: D J
authors.initials: DJ
authors.lastname: Beer
authors.forename: D
authors.initials: D
authors.lastname: Duquette
authors.forename: W W
authors.initials: WW
authors.lastname: Cruikshank
authors.forename: A S
authors.initials: AS
authors.lastname: Antonov
authors.forename: Y A
authors.initials: YA
authors.lastname: Romanov
authors.forename: V N
authors.initials: VN
authors.lastname: Smirnov
authors.forename: H W
authors.initials: HW
authors.lastname: Farber
mesh_terms: D000328:Adult; D002455:Cell Division; D002630:Chemotactic Factors / Q000378:metabolism / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011990:Receptors, Transferrin / Q000096:biosynthesis; D012701:Serotonin / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects*
chemical_list: D002630:Chemotactic Factors; D016207:Cytokines; D006133:Growth Substances; D006684:HLA-DR Antigens; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D012701:Serotonin