Regulation of the production and function of granulocytes and monocytes

The bone marrow responds to infection by rapidly producing mature granulocytes and monocytes from a small pool of committed progenitor cells under the influence of a heterogeneous family of glycoproteins termed colony-stimulating factors (CSFs). There are at least four major CSFs (IL-3, GM-, G-, and M-CSF) which are structurally distinct but have a great deal of functional overlap. The humoral signals which regulate the production of CSFs are generated at peripheral sites of infection through the activation of local macrophages and T lymphocytes by the invading pathogen. The monokines IL-1 and TNF are most likely the major humoral factors involved in stimulating CSF secretion by accessory cells in peripheral tissue sites as well as in the bone marrow microenvironment, although the functions of CSFs produced in these two organ compartments is distinct. CSFs secreted by bone marrow endothelial cells and fibroblasts serve to stimulate the proliferation and differentiation of myeloid progenitor cells, while CSFs present in areas of local infection are most likely involved in the activation of mature myeloid cell function. The dual ability of CSFs to both regulate bone marrow proliferation and to stimulate mature myeloid cell function represents a novel mechanism for producing a coordinated host response to infection.