Regulation of hematopoiesis

General classification principles

The process of blood cell maturation is under strict control. The main mechanism is humoral regulation. There are two large groups of regulatory molecules depending on the physiological effect they produce:

• Stimulators — trigger proliferation and cellular maturation.
• Inhibitors — suppress these processes to maintain homeostasis.

Depending on their spectrum of action, these factors can be general, meaning they affect the entire hematopoiesis process as a whole, or specific, which purposefully regulate the development of only one particular hematopoietic lineage (e.g., erythroid or thrombocytic).

Hemopoietins: hematopoietic stimulators

Humoral stimulators are grouped under the general term hemopoietins. Traditionally, they are divided into two categories, although in practice this division is quite conventional.

1. Colony-stimulating factors (CSFs). This group includes multi-CSF, erythropoietin (E-CSF), thrombopoietin, granulocyte CSF (G-CSF), and thymopoietins. Their main target is cells at early stages of development. The main task of CSFs is to set the vector of further differentiation for the immature cell.
2. Interleukins (ILs). This category includes substances from IL-1 to IL-7. They act on already relatively differentiated cellular elements, finely regulating their functional activity and capacity for division.

It is important to consider that the boundaries between these groups are blurred, and their biological action spectra often overlap. For example, multi-CSF can affect cells of completely different degrees of maturity — from the earliest stem cells to nearly fully formed ones. Another striking example is interleukin-3 (IL-3), whose presence is critically required at all stages and directions of hematopoiesis without exception.

To achieve the desired physiological effect, almost always not a single isolated factor is required, but rather their combination. Each hematopoietic pathway at a certain stage requires its own unique set of stimulators, while the same factor can participate in different combinations.

Sources of hemopoietin production

The synthesis of stimulating factors can occur both directly in the area of hematopoiesis and at a significant distance from it, operating on a hormonal principle.

• Local production (microenvironment). Most factors are produced directly within the hematopoietic organs. The sources include stromal cells, tissue macrophages, blood vessel endothelium, and even mature blood cells themselves (ensuring autocrine and paracrine types of regulation).
• Distant production. A number of substances are synthesized in other organs and delivered to the bone marrow systemically via the bloodstream. Thus, thrombopoietin is produced in the liver, and erythropoietin — predominantly in the kidneys, liver, and lungs (only a small portion is formed locally in the bone marrow).
• Interorgan regulation. Hemopoietins from one organ can distantly control another. For example, thymopoietins (endocrine products of the thymus) enter the red bone marrow, where they direct lymphopoiesis precursors strictly down the pathway of T-cell formation.
• Classical hormones. Hematopoiesis processes are also influenced by thyroid hormones (thyroxine) and the pituitary growth hormone (somatotropin).

Special attention should be paid to the stage-specific mechanism of action of thymus hormones (thymosin). It operates step-by-step in different localizations:

1. In the red bone marrow — stimulates the migration of pro-T-cells to the thymus.
2. In the thymus — triggers active proliferation of T-lymphoblasts.
3. In the peripheral lymphoid tissue — stimulates the multiplication of T-immunoblasts (this occurs already after meeting an antigen).

Hemopoiesis inhibitors

To maintain strict homeostasis, the circulatory system needs not only constant stimulation but also timely braking that switches on. This function is performed by inhibitors.

• Specific inhibitors (chalones). These substances are produced by mature blood cells. Their mechanism of action is based on the principle of negative feedback: the more mature formed elements accumulate in the bloodstream, the more strongly the chalones they release suppress the production of new cells in the bone marrow.
• Relatively nonspecific inhibitors. This group includes tissue hormones (such as prostaglandins and interferon) and true hormones, in particular glucocorticoids (produced by the adrenal cortex). Glucocorticoids play a key role in the body's stress responses: they are capable of strongly suppressing lymphopoiesis, which is morphologically manifested by a substantial decrease in the total volume of lymphoid tissue.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of autocrine and paracrine regulation of hematopoiesis
• The principle of the combined action of hemopoietins
• The role of macrophages and stromal cells in forming the microenvironment
• Hormonal influence of the thyroid gland and pituitary gland on hematopoiesis
• Detailed analysis of the stage-specific action of thymosin

Other topics in the section "Hematopoietic and lymphoid organs"

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