Role of annexin A1 in modulating granulopoiesis

Abstract

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)