Research

Kinin B₂ receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice

Adriana C Dos Santos¹ , Ester Roffê² , Rosa ME Arantes³ , Luiz Juliano⁴ , Jorge L Pesquero¹ , João B Pesquero⁴ , Michael Bader⁵ , Mauro M Teixeira² and Juliana Carvalho-Tavares¹

¹Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil

²Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil

³Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil

⁴Escola Paulista de Medicina, São Paulo, SP, Brazil

⁵Max Delbruck Center for Molecular Medicine, Berlin, Germany

author email corresponding author email

Journal of Neuroinflammation 2008, 5:49doi:10.1186/1742-2094-5-49

Published:	5 November 2008

Abstract

Background

Kinins are important mediators of inflammation and act through stimulation of two receptor subtypes, B₁ and B₂. Leukocyte infiltration contributes to the pathogenesis of autoimmune inflammation in the central nervous system (CNS), occurring not only in multiple sclerosis (MS) but also in experimental autoimmune encephalomyelitis (EAE). We have previously shown that the chemokines CCL2 and CCL5 play an important role in the adhesion of leukocytes to the brain microcirculation in EAE. The aim of the present study was to evaluate the relevance of B₂ receptors to leukocyte-endothelium interactions in the cerebral microcirculation, and its participation in CNS inflammation in the experimental model of myelin-oligodendrocyte-glycoprotein (MOG)_35–55-induced EAE in mice.

Methods

In order to evaluate the role of B2 receptor in the cerebral microvasculature we used wild-type (WT) and kinin B2 receptor knockout (B₂^-/-) mice subjected to MOG_35–55-induced EAE. Intravital microscopy was used to investigate leukocyte recruitment on pial matter vessels in B₂^-/- and WT EAE mice. Histological documentation of inflammatory infiltrates in brain and spinal cords was correlated with intravital findings. The expression of CCL5 and CCL2 in cerebral tissue was assessed by ELISA.

Results

Clinical parameters of disease were reduced in B₂^-/- mice in comparison to wild type EAE mice. At day 14 after EAE induction, there was a significant decrease in the number of adherent leukocytes, a reduction of cerebral CCL5 and CCL2 expressions, and smaller inflammatory and degenerative changes in B₂^-/- mice when compared to WT.

Conclusion

Our results suggest that B₂ receptors have two major effects in the control of EAE severity: (i) B₂ regulates the expression of chemokines, including CCL2 and CCL5, and (ii) B₂ modulates leukocyte recruitment and inflammatory lesions in the CNS.