Hematopoietic growth factor cytokines are specific glycoproteins that regulate and control hematopoiesis.
Functions of hematopoietic growth factor cytokines:-
Functions of hematopoietic growth factor cytokines:-
- Promote cell survival (suppress apoptosis).
- Promote proliferation.
- Control & regulate the processes of differentiation.
Characteristics of Growth Factors:-
- Produced by stromal cells in B.M. (except: Epo).
- Generally, more than one GP needed to control hematopoietic.
- React with specific membrane receptors.
- Affect hematopoiesis directly or indirectly.
- Act synergistically with each other.
- The majority have multiple biologic activities (not lineage specific).
- GP = Glycoprotein.
Early-Acting (Multilineage) GFs
- Act on multipotential precursor cells.
- SCF, FL, IL-3, GM-CSF, IL-6 & IL-11 .
SCF:
- SCF = Stem Cell Factor = Steel Factor “SF” = kit ligand “KL” = Mast Cell Growth Factor “MCGF” .
- Proliferation & differentiation of CFU-GEMM, CFU-GM, CFU-Mk, BFU-E.
- Also promotes the survival, proliferation & differentiation of mast cell precursors.
- Plays role in normal melanocyte development & gametogenesis.
Flt3 ligand (FL):
- Increases recruitment of primitive HSC into the cell cycle & inhibits apoptosis.
- Flt3 ligand has little effect on unilieage BFU-E/CFU-E, CFU-mast cell or CFU-Eo but it is a potent stimulator of granulocytic, B cell, & dendritic cell proliferation & differentiation.
- HSC = Hematopoietic Stem Cell.
IL-3:
- Affects multilineage progenitor cells & early commited progenitors like BFU-E.
- Also has indirect actions & can can induce the expression of other cytokines.
GM-CSF:
- Affects CFU-GEMM, BFU-E, CFU-Mk, CFU-GM, & CFU-Eo.
- GM-CSF: it is a major promoter of granulocyte & monocyte differentiation, but lacks a significant effect on basophil production.
- GM-CSF also activates the functional activities of most nature phagocytes, including neutrophils, macrophages & eosinophils.
IL-6 & IL-11:
- They are pleiotropic cytokines with overlapping growth stimulatory effects on myeloid & lymphoid cells as well as on primitive multilineage cells.
- Significant effects on megakaryopoiesis & platelet production.
- Both also mediate the acute phase response of hepatocytes. Also they are major pyrogens in vivo.
IL-11:
- Shortens the duration of G0 of primitive hematopoietic progenitor cell & hastens hematopoietic recovery after treatment with cytotoxic agents or B.M. transplantation.
Later-Acting (Lineage-Restricted) GFs
- G-CSF : granulocytes.
- M-CSF : monocytes. (Also regulates the genesis of osteoclasts).
- EPO : RBCs.
- TPO : megakaryocytes & platelets.
- IL-5 : eosinophils. (Also stimulates lymphocyte development).
- The other interleukins important in lymphopoiesis (ILs-2, -4, -7, -10, -12, -13, -14, -15).
Erythropoietin (EPO):
- The only cytokine to function as true hormone.
- Embryonic life: produced largely by liver.
- Adult life: largely produced by kidney (~ 90%), & by liver (to a lesser extent; ~ 10%).
- Production is regulated by the oxygen needs; induced by hypoxia.
- Stimulates growth, survival, & differentiation of erythroid progenitor cells (major effect on CFU-E); & stimulates proliferation & RNA synthesis in more well-differentiated maturing cells.
- Reticulocytes & mature erythrocytes do not have receptors for EPO; so they are not affected by EPO.
Thrombopoietin (TPO):
- TPO = mpl-ligand = megakaryocyte growth & development factor (MGDF). Megakaryocyte & platelet production.
- In vitro, make/primes mature platelets to respond to aggregation-inducing stimuli & increases the platelet release reaction.
- Act with a variety of other GFs (SCF, IL-3, FL) to stimulate the growth of primitive progenitor cell.
Indirect-Acting Growth Factors
- Some cytokines that regulate hematopoiesis do so indirectly.
- Example: IL-1 .
- IL-1: has no colony-stimulating activity itself, but it induces neutrophilic leukocytosis, resulting from the release of other direct-acting cytokines by accessory cells.
0 comments:
Post a Comment