Pharmacological Beta-Adrenergic Receptor Activation Attenuates Neutrophil Recruitment by a Mechanism Dependent on Nicotinic Receptor and the Spleen.
The aim of this study was to identify the effect of beta-adrenergic receptor activation on neutrophil migration in experimental peritonitis elucidating the neuroimmune components involved such as nicotinic receptors and the spleen. Mice pre-treated with mecamylamine (nicotinic antagonist) and propranolol (beta-adrenergic antagonist) or splenectomized animals were treated with isoproterenol (beta-adrenergic agonist) prior to intraperitoneal injection of carrageenan. After 4 h, the infiltrating neutrophils and the local cytokine/chemokine levels were evaluated in the peritoneal lavage. The effect of isoproterenol on neutrophil chemotaxis was investigated in a Boyden chamber. Isoproterenol inhibited neutrophil trafficking, reducing the cytokine/chemokine release and neutrophil chemotaxis. Surprisingly, the isoproterenol effect on neutrophil migration was totally reverted by splenectomy and mecamylamine pre-treatment. In contrast, the inhibitory effect of nicotine on neutrophil migration was abrogated only by splenectomy but not by propranolol pre-treatment. Collectively, our data show that beta-adrenergic receptor activation regulates the acute neutrophil recruitment via splenic nicotinic receptor.
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Vila Monte Alegre, 14049-900, Ribeirão Preto, SP, Brazil. rangel.leal@usp.com.
Rangel L
RL
Silva
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Vila Monte Alegre, 14049-900, Ribeirão Preto, SP, Brazil.
Fernanda V
FV
Castanheira
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Vila Monte Alegre, 14049-900, Ribeirão Preto, SP, Brazil.
Jozi G
JG
Figueiredo
Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.
Gabriel S
GS
Bassi
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Vila Monte Alegre, 14049-900, Ribeirão Preto, SP, Brazil.
Sérgio H
SH
Ferreira
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Vila Monte Alegre, 14049-900, Ribeirão Preto, SP, Brazil.
Fernando Q
FQ
Cunha
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Vila Monte Alegre, 14049-900, Ribeirão Preto, SP, Brazil.
Thiago M
TM
Cunha
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Vila Monte Alegre, 14049-900, Ribeirão Preto, SP, Brazil. alex_bioquimica@yahoo.com.br.
Alexandre
A
Kanashiro
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000032:analysis; D007545:Isoproterenol / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010538:Peritonitis; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013154:Spleen / Q000737:chemistry / Q000378:metabolism; D013156:Splenectomy
D000318:Adrenergic beta-Agonists; D016207:Cytokines; D018733:Nicotinic Antagonists; D011943:Receptors, Adrenergic, beta; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D007545:Isoproterenol
beta-adrenergic receptor; isoproterenol; neuroimmunomodulation; neutrophil; nicotinic receptor