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Role of annexin A1 in modulating granulopoiesis

Grant number: 16/02903-6
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): May 01, 2016
Effective date (End): April 30, 2018
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Sandra Helena Poliselli Farsky
Grantee:Christiano Marcello Vaz Barbosa
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:14/07328-4 - Identification of endogenous pathways for the control of inflammation, AP.TEM


Annexin A1 (ANXA1) is a 37 kDa protein and plays a role in diverse cellular functions, such as phagocytosis, proliferation, apoptosis, inflammation and signal transduction. Recently, our group, in association with Drs. Roderick Flower and Mauro Perretti from William Harvey Research Institute, University of London, have shown the role of ANXA1 on the actions of endogenous glucocorticoids upon neutrophil traffic and granulopoiesis. We observed that ANXA1 controls the actions of glucocorticoid on expression of adhesion molecule into neutrophils and endothelial cells, modulates neutrophil mobilization from the bone marrow (BM) into the blood and the phagocytosis of BM homing apoptotic neutrophils by BM macrophage. We also demonstrate that ANXA1 is constitutive protein into BM granulocyte during differentiattion; controls the SDF-1± secretion by stromal cells and regulates the activation of CXCR-4 receptor. Furthermore, we verify that ANXA1 knockout mice (ANXA1-/-) have reduced the number of CFU-GM, increased the number of neutrophils and increased of Ly6G expression marker in the BM. Based on our data, the propose of this work, which is associated to the thematic project "Identification of endogenous pathways for the control of inflammation" (2014/07328-4), is to evaluate the effect of ANXA1 in the granulocytic differentiation, now mapping the myeloid differentiation cascade using immunophenotyping markers for HSC and myeloid progenitor cells (MPP, CMP, GMP, MEP), differentiation markers, functional capacity and competitive reconstitution assays. (AU)

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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)
BARBOSA, V, CHRISTIANO M.; FOCK, RICARDO AMBROSIO; HASTREITER, ARACELI APARECIDA; REUTELINGSPERGER, CRIS; PERRETTI, MAURO; PAREDES-GAMERO, EDGAR J.; FARSKY, SANDRA H. P.. Extracellular annexin-A1 promotes myeloid/granulocytic differentiation of hematopoietic stem/progenitor cells via the Ca2+/MAPK signalling transduction pathway. CELL DEATH DISCOVERY, v. 5, . (16/02903-6, 14/07328-4)

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