Lineage-specific Cytokine Regulation

LINEAGE-SPECIFIC CYTOKINE REGULATION

Erythropoiesis:

In the erythroid lineage, progenitor cells give rise to two distinct types of erythroid colonies in culture. A primitive progenitor cell, the BFU-E, is relatively insensitive to EPO and forms large colonies after 14 days in the form of bursts. Production of BFU-E colonies was originally described as being supported by burst-promoting activity, or BPA, now known to be IL-3 or GM-CSF. CFU-E colonies grow to maximal size in 7 to 8 days and depend primarily on EPO. The CFU-E are the descendants of BFU-E and subsequently give rise to the first recognizable erythrocyte precursor, the pronormoblast. Other cytokines reported to influence production of red cells include IL-9, IL-11, and SCF. However, EPO is the pivotal humoral factor that functions to prevent apoptosis and induce proliferation/differentiation of the most committed erythroid progenitor cells and their progeny.

Granulopoiesis and Monopoiesis:

Granulocytes and monocytes are derived from a common bipotential progenitor cell, the CFU-GM, derived from CFUGEMM. Specific GFs for granulocytes and monocytes, acting synergistically with GM-CSF and/or IL-3, support the differentiation pathway of each lineage. M-CSF supports monocyte differentiation while G-CSF induces neutrophilic granulocyte differentiation. Eosinophils and basophils also are derived from the CFU-GEMM under the influence of growth factors IL-5 and IL-3/IL-4, respectively.

Megakaryocytopoiesis/Thrombopoiesis:

Platelets are derived from megakaryocytes, which are progeny of the CFU-EMk. CFU-Mk are induced to proliferate and differentiate into megakaryocytes by several cytokines. However, the cytokines that induce the greatest increase in platelet production are IL-11 and TPO.

Lymphopoiesis:

The growth and development of lymphoid cells from the common lymphoid progenitor cell occurs in multiple anatomic locations including the bone marrow, thymus, lymph nodes, and spleen. Multiple GFs play a role in T and B lymphocyte growth and development, most of which act synergistically.