Bradykinin B-1 receptor expression and function on T lymphocytes in activemultiple sclerosis

Background: Lesion development in MS is initiated by migration of inflammat ory cells into the central nervous system, a process dependent on endotheli al cell-lymphocyte interaction. Bradykinin B-1 receptor is a membrane-bound G protein-coupled receptor shown to be upregulated on the surface of vario us cells types during inflammation. Objective: To assess the expression and function of the bradykinin B-1 receptor on T lymphocytes from MS patients. Methods: The authors used multiplex polymerase chain reaction amplificatio n and Western blot techniques to demonstrate B-1 receptor expression by T c ells. A modified Boyden chamber assay also was used to assess the effect of B-1 agonist and antagonist on T cell migration. Results: The authors demon strated that the expression of B-1 receptor was upregulated on T cells deri ved from peripheral blood of MS patients. Expression of this receptor was u pregulated on T cells from patients with secondary progressive MS and relap sing-remitting patients in active relapse. Expression was lower in relapsin g-remitting patients in remission and least in control subjects, including patients with epilepsy, chronic inflammatory demyelinating polyneuritis, an d systemic lupus erythematosus. In vitro treatment of cells from healthy co ntrol subjects with tumor necrosis factor-alpha and interferon-gamma also i nduced the expression of B-1 receptors. The authors also found that the sig nificantly higher rate of migration of MS T lymphocytes, compared with cont rol subjects in the Boyden chamber assay, could be prevented by the additio n of the selective and stable B-1 agonist Sar (D-Phe(8)) desArg(9)-BK. Conc lusion: The authors demonstrate that B-1 receptors are upregulated by T lym phocytes during the course of MS and that signaling through this receptor w ith a B-1 agonist can negatively regulate T-cell migration in vitro.