INVESTIGAÇÃO DA PARTICIPAÇÃO DO RECEPTOR PURINÉRGICO P2X7 NA REGULAÇÃO DA CÉLULA-TRONCO HEMATOPOÉTICA E LINHAGENS MIELOIDES

Abstract

Hematopoietic stem cells (HSCs) are multipotent cells that are essential for the blood and lymphatic systems due to their high potential to repopulate the bone marrow and generate all cell types of these systems. Therefore, understanding the regulatory mechanisms of HSCs and identifying molecules that allow the manipulation of this population is of great scientific and clinical relevance. Intracellular pathways that control HSCs self-renewal and differentiation have been investigated, using hematopoietic cytokines and purinergic receptors as activators. This study aims to elucidate the role of purinergic receptors in regulating HSC and myeloid differentiation. We focus on the P2X7 receptor using a knockout mouse model and compare it to a wild-type animal. The P2X7 receptor is an ATP-gated cationic channel, and its prolonged activation leads to the formation of a non-selective membrane macropore, an activity primarily associated with the immune system. Using material obtained from peripheral blood and bone marrow cells, we analyzed hematological parameters, quantified cell populations, assessed colony-forming ability, measured inflammatory cytokines, and oxidative stress. We observed alterations in HSC, GMP, lymphoid progenitors, and myeloid cells. This opens up a path for further exploration of the P2X7 receptor in hematopoiesis, as well as compensatory mechanisms involving other purinergic receptors.