Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis

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.

Mercury Chloride Impacts on the Development of Erythrocytes and Megakaryocytes in Mice

“…Erythrocytes are turned over periodically in vivo, depending on the balance between the clearance of senescent erythrocytes in the periphery and newly generated erythrocytes in the BM [ 16 , 18 ]. HgCl 2 increased the number of progenitors for erythrocytes and megakaryocytes in the BM but did not impact the clearance of RBCs in B10.S mice, indicating that the increased number of mature RBCs and platelets in the blood was due to increased erythro-megakaryopoiesis in B10.S during HgCl 2 exposure.…”

“…Environmental pollutants can significantly impact hematopoiesis [ 17 , 18 ]. We previously reported that heavy metals in the living environment such as cadmium, lead, and Hg significantly influenced the function of HSCs and the committed progenitors, leading to aberrant myelopoiesis and/or lymphopoiesis [ 19 , 20 , 21 , 22 , 23 ].…”

Heavy Metals in the Environment and Thyroid Cancer

“…In vitro, there were no effects in human thyroid cell morphology, viability, or proliferation when thyrocytes in primary cultures were chronically (72 h) exposed to several heavy metals (Cd, Cu, Hg, Mn, Pd, W, and Zn) at concentrations that are 0.1-100-fold relative to those measured in the urines of residents of the volcanic area. Based on previous observations [45][46][47][48] that immature progenitor cells may be more sensitive to the toxic effect of pollutants, we tested the same heavy metals, at the same low concentrations, in undifferentiated human thyrocytes in the form of thyrospheres. Thyrospheres are aggregates of thyroid stem cells and precursors of thyrocytes at a different level of differentiation [49] that, depending on the culture conditions, are able to differentiate into mature thyrocytes or produce additional thyrospheres by a process involving stem cells and named selfrenewal [50].…”

The potential interaction of environmental pollutants and circadian rhythm regulations that may cause leukemia

“…The genes of circadian rhythms are affected by several chemical environmental pollutants that have been associated with the development of leukemias such as benzene, cigarette smoke, some pesticides and microplastics, although for some of them there is still not enough data to be considered as risk factors (Table 2). Given that leukemia is a disease that is favored by several factors for its development (multifactorial) (Belson et al, 2007;Buffler et al, 2005;Davis et al, 2014), it is possible that the presence of environmental pollutants that affect circadian rhythms can contribute, to some extent, in people to make them more susceptible to developing leukemia (Scharf et al, 2020). In addition, it is not yet known whether the effects of environmental pollutants, or their mixtures (synergistic effects), on leukemic cells and circadian rhythms, also affect the efficacy of the therapeutic drugs used against this disease.…”