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The role of cholinergic anti-inflammatory pathway in the neutrophil migration in model of experimental peritonitis

Grant number: 13/01466-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2013
Effective date (End): October 31, 2014
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal researcher:Alexandre Kanashiro
Grantee:Matheus Christovam Mangetti
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:11/20343-4 - Antiinflammatory cholinergic pathway: the role of neuroimmunomodulation in the control of inflammatory response, AP.JP


The migration of neutrophils related to inflammation of tissues is a critical event in maintaining homeostasis and is essential to the organic responses against invading pathogens. This process occurs due to (I) release of inflammatory mediators (chemokines and cytokines) by resident macrophages, (II) expression of adhesion molecules, which cause the rolling and adhesion of neutrophils to endothelial cells, and (III) transmigration of these cells into the extra-vascular space. On the other hand, the excessive release of neutrophil leads to tissue damage, as observed in chronic inflammatory processes, such as autoimmune diseases. Therefore, the regulation of migration of neutrophils has become an important strategy in the treatment of inflammatory pathological conditions. Recently, several studies have established that both immune and central nervous systems (CNS) communicate with each other through an elaborated axis and bidirectional neuro-immune controls the CNS immune responses by dependent mechanisms on the parasympathetic autonomic system / sympathetic in called "cholinergic anti-inflammatory pathway". Thus, this project aims at investigating the role of activation / blockade of cholinergic anti-inflammatory pathway (with emphasis on beta-adrenergic receptors and nicotinics) on neutrophil migration in models of peritonitis, using for this purpose different surgical strategies (vagotomy , splenectomy) and / or pharmacological (agonists / antagonists beta-adrenergic/nicotinics, nicotinic derivatives, sympatholytic drugs, etc.). In this project, we will investigate (i) migration of neutrophils (measured by total and differential counts of peritoneal lavage), (ii) expression of adhesion molecules on neutrophils and endothelial tissue, (iii) adhesion and rolling, (iv) vascular permeability ( measured by Evans blue) and (v) local production of cytokines / chemokines. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SILVA, RANGEL L.; CASTANHEIRA, FERNANDA V.; FIGUEIREDO, JOZI G.; BASSI, GABRIEL S.; FERREIRA, SERGIO H.; CUNHA, FERNANDO Q.; CUNHA, THIAGO M.; KANASHIRO, ALEXANDRE. Pharmacological Beta-Adrenergic Receptor Activation Attenuates Neutrophil Recruitment by a Mechanism Dependent on Nicotinic Receptor and the Spleen. Inflammation, v. 39, n. 4, p. 1405-1413, AUG 2016. Web of Science Citations: 2.

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