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

Abstract

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 B₁ 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 B₁ receptor on T lymphocytes from MS patients.

Methods: The authors used multiplex polymerase chain reaction amplification and Western blot techniques to demonstrate B₁ receptor expression by T cells. A modified Boyden chamber assay also was used to assess the effect of B₁ agonist and antagonist on T cell migration.

Results: The authors demonstrated that the expression of B₁ 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-α and interferon-γ also induced the expression of B₁ 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 B₁ agonist Sar (D-Phe⁸) desArg⁹-BK.

Conclusion: The authors demonstrate that B₁ receptors are upregulated by T lymphocytes during the course of MS and that signaling through this receptor with a B₁ agonist can negatively regulate T-cell migration in vitro.