Abstract
Hematopoiesis is a complex and intricate process that aims to replenish blood components in a constant fashion. It is orchestrated mostly by hematopoietic progenitor cells (hematopoietic stem cells (HSCs)) that are capable of self-renewal and differentiation. These cells can originate other cell subtypes that are responsible for maintaining vital functions, mediate innate and adaptive immune responses, provide tissues with oxygen, and control coagulation. Hematopoiesis in adults takes place in the bone marrow, which is endowed with an extensive vasculature conferring an intense flow of cells. A myriad of cell subtypes can be found in the bone marrow at different levels of activation, being also under constant action of an extensive amount of diverse chemical mediators and enzymatic systems. Bone marrow platelets, mature erythrocytes and leukocytes are delivered into the bloodstream readily available to meet body demands. Leukocytes circulate and reach different tissues, returning or not returning to the bloodstream. Senescent leukocytes, specially granulocytes, return to the bone marrow to be phagocytized by macrophages, restarting granulopoiesis. The constant high production and delivery of cells into the bloodstream, alongside the fact that blood cells can also circulate between tissues, makes the hematopoietic system a prime target for toxic agents to act upon, making the understanding of the bone marrow microenvironment vital for both toxicological sciences and risk assessment. Environmental and occupational pollutants, therapeutic molecules, drugs of abuse, and even nutritional status can directly affect progenitor cells at their differentiation and maturation stages, altering behavior and function of blood compounds and resulting in impaired immune responses, anemias, leukemias, and blood coagulation disturbances. This review aims to describe the most recently investigated molecular and cellular toxicity mechanisms of current major environmental pollutants on hematopoiesis in the bone marrow.
Highlights
Hematopoiesis is a complex and intricate process that aims to replenish blood components in a constant fashion
GMP differentiation is dependent on secretion of granulocyte-macrophage-colony-stimulating factor (GM-CSF), after which macrophage-colony-stimulating factor (M-CSF) modulates the differentiation of monocytes/macrophages and granulocyte-colony-stimulating factor (G-CSF) modulates the differentiation of neutrophils, basophils, and eosinophils; the latter in a process known as granulopoiesis
megakaryocyte-erythrocyte progenitors (MEPs) differentiates into burst-forming unit erythroid (BFU-E) and, into colony-forming unit erythroid (CFU-E); this whole process is tightly modulated by soluble mediators such as erythropoietin (EPO), stem cell factor (SCF), and IL-3 and -6
Summary
Hematopoiesis is a continuous, albeit complex, process that aims to generate blood cell subtypes in a steady manner. Hematopoietic stem cells (HSCs) represent a small population of pluripotent, self-renewing cells responsible for initiating the renewal of blood cells by giving rise to other cell progenitors. In humans, such cells are CD34+CD38− [1]. In bone marrow (BM), HSCs initially give rise to multipotent progenitors (MPPs), which can be considered pluripotent These cells have limited self-renewal capabilities, yet possess full-lineage differentiation potential [2]. MPPs differentiated into CLPs originate lymphocytes and natural killer cells that rely mainly on activation of PU., Ikaros and GATA-3 transcription factors [7]. Disruption of these molecular pathways leads to anemia and myeloproliferative syndromes [6,11,12]
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