Regulatory Factors

The regulatory factors for hematopoiesis (see Table 15-11) comprise classical hormones, growth factors, and cytokines, which control and direct the division and maturation of the hematopoietic process down

Bradykinin

Bradykinin

Nitrovasodilators

Endothelium

Nitrovasodilators

Endothelium

Smooth muscle

Smooth muscle

FIGURE 15-18 Model for the synthesis of NO in endothelial cells and its paracrine actions in smooth muscle cells. In (A), shear stress or receptor activation of vascular endothelium by bradykinin or acetylcholine results in an influx of calcium. The consequent increase in intracellular calcium stimulates the constitutive nitric oxide synthase (NOS). The nitric oxide (NO) formed from L-arginine (L-Arg) by this enzyme diffuses to nearby smooth muscle cells, in which it stimulates the soluble guanylate cyclase (sGC), resulting in enhanced synthesis of cyclic GMP from guanosine triphosphate (GTP). This increase in cyclic GMP in the smooth muscle cells leads to their relaxation. In (B), nitrovasodilators such as sodium nitroprusside and nitroglycerin release nitric oxide spontaneously or through an enzymatic reaction. The liberated nitric oxide stimulates the soluble guanylate cyclase in the vascular smooth muscle cell, resulting in relaxation. Adapted from Moncada, C., and Higgs, A. (1993). The L-arginine-nitric oxide pathway. New Engl. J. Med. 329, 2002-2012.

eight possible paths of cell development (see Figure 15-20).

1. Cytokines

Cytokines are peptide hormones produced mainly by macrophages and lymphocytes, but also by leucocytes and fibroblasts present in the erythron. Most cytokines act in a paracrine or autocrine fashion. They function in the complex cell differentiation process of hematopoiesis (see Table 15-11) and are also involved in the processes of inflammation and immune reactions; the latter topic is not discussed in this chapter.

The regulatory actions of each of the cytokines upon hematopoiesis are mediated by unique receptors pres ent in the cell membranes of the responding cells. Typically these are transmembrane glycoproteins; collectively they belong to a superfamily of cytokine growth factor receptors that also includes the receptors for growth hormone and prolactin (see Figure 15-21).

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