Bradykinin B1 receptor expression and function on T lymphocytes in active multiple sclerosis

Background: Lesion development in MS is initiated by migration of inflammatory cells into the central nervous system, a process dependent on endothelial cell-lymphocyte interaction. Bradykinin B-1 receptor is a membrane-bound G protein-coupled receptor shown to be upregulated on the surface of various 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 amplification and Western blot techniques to demonstrate B-1 receptor expression by T cells. 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 demonstrated that the expression of B-1 receptor was upregulated on T cells derived from peripheral blood of MS patients. Expression of this receptor was upregulated on T cells from patients with secondary progressive MS and relapsing-remitting patients in active relapse. Expression was lower in relapsing-remitting patients in remission and least in control subjects, including patients with epilepsy, chronic inflammatory demyelinating polyneuritis, and systemic lupus erythematosus. In vitro treatment of cells from healthy control subjects with tumor necrosis factor-alpha and interferon-gamma also induced the expression of B-1 receptors. The authors also found that the significantly higher rate of migration of MS T lymphocytes, compared with control subjects in the Boyden chamber assay, could be prevented by the addition of the selective and stable B-1 agonist Sar (D-Phe(8)) desArg(9)-BK. Conclusion: The authors demonstrate that B-1 receptors are upregulated by T lymphocytes during the course of MS and that signaling through this receptor with a B-1 agonist can negatively regulate T-cell migration in vitro.