Figure 2. Myeloid cell recruitment, activation, and regulation.

Pluripotent stem cells differentiate into myeloid progenitors in the bone marrow where, under the influence of growth and colony stimulating factors, the cells differentiate into monoblasts. Monoblasts in turn develop into monocytes and migrate from the bone marrow into the blood where they circulate for several days and then are distributed to the tissues either as resident macrophages or as recruited macrophages at sites of infection and inflammation. Resident macrophages are phenotypically and functionally influenced by their environment, which varies with the anatomical location. During an inflammatory reaction, circulating monocytes adhere and migrate across the endothelium in response to chemoattractant gradients generated by stromal and inflammatory cells. Depending on the extracellular milieu, the cells may become polarized, exhibiting characteristics of M1 and/or M2 macrophages.