Role of endogenous glucocorticoids and annexin A1 on neutrophil migration: involvement of SDF1 alpha/CXCR-4 and IL-17/IL-23

• Grant number: 10/08402-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2010
• End date: December 31, 2013
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Sandra Helena Poliselli Farsky
• Grantee: Isabel Daufenback Machado
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The traffic of leukocytes in the body is a key issue for the innate and the adaptive immune response. This process is complex, dependent on the action of many chemicals substances, further the perfect cell interactions. Among the complexity involved in the traffic of neutrophils from bone marrow into blood, there is evidence of involvement of the SDF-1alfa/CXCR-4 and IL-17, IL-23, G-CSF axes, which regulate the production and release of neutrophils, and the involvement of adhesion molecules integrins (CD18 and CD49d) and selectin CD62L. It has been shown that glucocorticoids (GC) modulate the traffic of neutrophils and the mechanisms of this control can be differently mediated, depending on the circulating concentration of these hormones. Therefore, this study aims to evaluate the action of endogenous GC (eGC) and the annexin-A1 (ANXA1), a protein secreted by the action of GC, on SDF-1alfa/CXCR-4 and IL-17/IL23 axes and on the expression of adhesion molecules. Male Swiss mice, and Balb/C wild types (WT) or knockout (ANXA1-/ -) will be employed. Evaluations will be performed at baseline condition and at high concentrations of eGC, evoked by LPS induced inflammation or by administration of ACTH. Total and differential numbers of bone marrow and blood cells will be quantified in Neubauer chamber and stained smears by May-Grunwald and their CXCR-4, CD62L, CD49 and CD18 expressions will be measured by flow cytometry. Concentrations of chemical mediators IL-17, IL-23, G-CSF and SDF-1 alfa will be quantified by ELISA in the bone marrow perfusate and plasma. Our group has recently shown, in collaboration with Dr. Mauro Perretti, from the William Harvey Institute of London, and Dr Sara Rankin, from Imperial College London, the physiological role of ANXA1 in the axis SDF-1alfa/ CXCR-4. Thus, this project will broaden the knowledge of the mechanisms of GC on the pathways involved in neutrophil traffic.

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)

MACHADO, ISABEL DAUFENBACK; SANTIN, JOSE ROBERTO; DREWES, CARINE CRISTIANE; GIL, CRISTIANE DAMAS; OLIANI, SONIA MARIA; PERRETTI, MAURO; POLISELLI FARSKY, SANDRA HELENA. Alterations in the profile of blood neutrophil membrane receptors caused by in vivo adrenocorticotrophic hormone actions. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 307, n. 9, p. E754-E763, NOV 1 2014. (10/16828-0, 10/19802-1, 10/17175-0, 10/08402-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MACHADO, Isabel Daufenback. Molecular mechanisms of endogenous glucocorticoid and annexin-a1 actions on neutrophil traffic: characterization of this action on the SDF-1α/CXCR4 e IL-17/IL23/G-CSF axis. 2013. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.