Serotonin-stimulated aortic endothelial cells secrete a novel T lymphocyte chemotactic and growth factor.
Atherosclerotic lesions contain multiple cell types including smooth muscle cells, macrophages, and T lymphocytes. The development of an extralymphatic T lymphocyte focus of inflammation in this condition requires chemoattractant-induced cell migration and growth factor-induced cell activation. In a previous study, we described a novel 13-15-kDa T lymphocyte-specific chemotactic cytokine, endothelial cell-derived lymphocyte chemoattractant activity (ED-LCA), secreted by serotonin-stimulated bovine aortic endothelial cells that is distinct from previously identified endothelial cell-derived interleukins (IL) 1, 6, and 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. We assessed 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 the p55 subunit of IL-2R, a threefold increase in TFR, and a twofold increase in HLA-DR. Passage into the G1 phase of the cell cycle was confirmed by cell cycle analysis employing acridine orange. Evaluation of CD4+ and CD8+ T cell subsets by double-antibody labeling demonstrated that the p55 subunit of IL-2R was induced in both T cell subsets. Although incubation of human T cells with ED-LCA alone did not induce proliferation, addition of exogenous IL-2 to T cells pulsed with ED-LCA for 24 h caused a proliferative response with a stimulation index of 3. By up-regulating functional cell surface receptors for IL-2, ED-LCA is a competence growth factor for T lymphocytes and primes them to respond to IL-2. 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 recruitment and amplification of the extralymphatic T cell component of atherosclerosis.
Katz
M F
MF
Pulmonary Center, Boston University School of Medicine, Massachusetts.
Farber
H W
HW
Dodds-Stitt
Z
Z
Cruikshank
W W
WW
Beer
D J
DJ
D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002453:Cell Cycle; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology; D012313:RNA / Q000032:analysis / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D011990:Receptors, Transferrin / Q000032:analysis; D012701:Serotonin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure
D002630:Chemotactic Factors; D006133:Growth Substances; D006684:HLA-DR Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D012701:Serotonin; D012313:RNA