Monocytes are considered to be immature macrophages, and the two types have been considered part of the reticulo-endothelial system (RES) or mononuclear phagocyte system (MPS).

Monocytes play a central role in coordinating immune responses by secreting cytokines and prostaglandins. Cytokines, particularly IL-1, amplify the antigen-induced activation of T cells, whereas released prostaglandins such as PGE2 are potent inhibitors of activation.

Monocytopoiesis takes place in the bone marrow:
stem cell → committed stem cell (common myeloid progenitor) → monoblast → promonocyte → monocyte (bone marrow) → monocyte (peripheral blood) → macrophage or myeloid dendritic cell (tissue).

Monocyte differentiation in the bone marrow requires 1.5 to 3 days. Three glycoprotein growth factors initiate the bone marrow differentiation of macrophages from uni- and bipotential progenitor cells. IL-3 controls the progression from pluripotential stem cell to myeloid-restricted progenitor. IL-3 generates differentiated progeny of all myeloid lineages, and as IL-3-responsive progenitors differentiate, they became responsive to GM-CSF and M-CSF, the two growth factors that determine monocyte/macrophage-restricted progeny. Following commitment to their lineage, monocytes and macrophages remain dependent on these growth factors for continued proliferation and viability. TNF-α, a member of the TNF-receptor superfamily, has also been implicated in growth regulation for macrophage precursors.

Some neutrophilic granules form in the monocyte cytoplasm during development, but these are fewer than those of neutrophil (neutrophilic granulocytes). Circulating monocytes possess migratory, chemotactic, pinocytic, and phagocytic capabilities, in addition to having receptors for IgG Fc-domains (FcR) and iC3b complement. Following migration into tissues, monocytes undergo further differentiation to become multifunctional tissue macrophages.

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