Author:
Dos Santos Adriana C,Roffê Ester,Arantes Rosa ME,Juliano Luiz,Pesquero Jorge L,Pesquero João B,Bader Michael,Teixeira Mauro M,Carvalho-Tavares Juliana
Abstract
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 MOG35–55-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.
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology,Immunology,General Neuroscience
Reference66 articles.
1. Couture R, Lindsey CJ: Brain kallikrein-kinin system: from receptors to neuronal pathways and physiological functions. Handbook of chemical anatomy. Edited by: Quirion R, BjõrklundA, Hõkfeld T. 2000, 16: 241-298.
2. Couture R, Harrison M, Vianna RM, Cloutier F: Kinin receptors in pain and inflammation. Eur J Pharmacol. 2001, 429: 161-176. 10.1016/S0014-2999(01)01318-8.
3. Ahluwalia A, Perretti M: B1 receptors as a new target. Could this B the 1?. TiPS. 1999, 20: 100-103.
4. Lehmberg J, Beck J, Baethmann A, Uhl E: Bradykinin antagonists reduce leukocyte endothelium interactions after global cerebral ischemia. J Cerebral Blood Flow & Metab. 2003, 23: 441-448. 10.1097/00004647-200304000-00008.
5. Prat A, Weinrib L, Becher B, Poirier J, Duquette P, Couture R, Antel JP: Bradykinin B1 receptor expression and function on T lymphocytes in acute multiple sclerosis. Neurology. 1999, 53: 2087-2092.
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