he ma to poiesis
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fk uisu al manarTRANSCRIPT
HEMATOPOIESIS
Erwin TaherFK UISU Al-Manar
M E D A N
Introduction
• In the fetus, hematopoiesis takes place initially in the yolk sac and later in the liver and the spleen.
• Islands of hematopoiesis develop in these tissues and then involute as the marrow becomes the primary site for blood cell formation by the seventh month of fetal development.
Tempat Berlangsungnya Haemopoiesis
• Yolk sac
• Liver dan spleen
• Bone marrow
Gambar :Tahapan pembentukan sel darah (hematopoiesis) yang dihubungkan dengan perjalanan umur
The term medullary hematopoiesis refers to the production of blood cells in the bone marrow. extramedullary hematopoiesis indicates blood cell production outside the marrow in the spleen, liver, and other locations.
ORGANIZATION OF HEMATOPOIETIC TISSUES
• The medullary space in which hematopoietic cells develop contains, normally, many adipocytes and a rich vascular supply
• Vascular endothelial cells, marrowfibroblasts, and stromal cells are important sources for the matrix proteins that provide structure to the marrow space and for production of the hematopoietic growth factors that stimulate cell proliferation.
• The vascular endothelial cells also form an important barrier that keeps immature cells in the marrow and permits mature hematopoietic elements to enter the blood.
• The adipocytes may influence hematopoiesis through their effects on the metabolism of androgens and estrogens.
• Marrow macrophages serve to remove effete or apoptotic cells, as well as to clear the blood of foreign materials when it enters the marrow.
• Osteoblasts and osteoclasts maintain and remodel the surrounding cancellous bone and the calcified lattice, which crisscrosses the marrow space.
• The thymus, lymph nodes, mucosa-associated lymphatic tissues (MALT), and the spleen have multiple hematopoietic functions.
-Early in development, they are major sites for hematopoiesis.
-In adulthood, they are principally sites for lymphocyte development, processing of antigens, development of effector T cells, and antibody production
Architecture of Bone Marrow
Hematopoietic Stem Cells
• All cells of the hematopoietic system are derived from common precursor cells, the hematopoietic stem cells.
• These cells are difficult to identify, in part because they normally represent only about 0.05 percent of marrow cells.
Pattern for Development of Blood Cells
BFU-E: burst-forming unit-erythroid; CFU-GM: colony-forming unit-granulocyte-macrophage; CFU-mega: colony-forming unit-megakaryocyte; EPO: erythropoietin; FLT-3L: fms-like tyrosine kinase-3 ligand; G-CSF: granulocyte colony-stimulating factor; GM-CSF: granulocyte-macrophage colony-stimulating factor; IL: interleukin; M-CSF: macrophage colony-stimulating factor; TPO: thrombopoietin; SCF: stem cell factor)
• Many aspects of the earliest steps in this differentiation process are not well understood.
• With lineage commitment, however, differentiation, maturation, and release of cells to the blood come under the control of well-defined hematopoietic growth factors.
• growth factors have overlapping activities for the early phases of differentiation.Later in development, some growth factors are lineage specific, meaning that they govern the maturation and deployment of single lineages. Erythropoietin (EPO), thrombopoietin (TPO), and granulocyte colony-stimulating factor (G-CSF) are the best-characterized lineage-specific factors.
Hematopoietic Growth Factors
• The hematopoietic growth factors, also referred to as hematopoietic cytokines, are a family of glycoproteins produced in the bone marrow by endothelial cells, stromal cells, fibroblasts, macrophages, and lymphocytes and also produced at distant sites from which they are transported to the marrow through the blood.
• Hematopoietic growth factors not only stimulate
cell proliferation but also prolong cell survival; that is, they have antiapoptotic effects.
Factor Other Names Cell Source ChromosomeLocation
Function
EPO Erythropoietin Juxtaglomerular cells 7q Stimulates erythrocyte formation and release from marrow
TPO Thrombopoietin; megakaryocytegrowth and development factor
Hepatocytes, renal andendothelial cells, fibroblasts
3q27 Stimulates megakaryocyteproliferation and plateletformation
G-CSF Granulocyte colony-stimulatingfactor; filgrastim; lenograstim
Endothelial cells, monocytes,fibroblasts
17q11.2-q21 Stimulates formation and functionof neutrophils
GM-CSF Granulocyte-macrophagecolony-stimulating factor
T cells, monocytes, fibroblasts
5q23-q31 Stimulates formation andfunction of neutrophils,monocytes, and eosinophils
M-CSF Macrophage colony-stimulatingfactor; colony stimulatingfactor–1 (CSF-1)
Endothelial cells,macrophages, fibroblasts
5q33.1 Stimulates monocyte formationand function
IL-1a andIL-1b
Interleukin-1a and -1b,endogenous pyrogenhemopoietin-1
Monocytes, keratinocytes,endothelial cells
2q13 Proliferation of T cells, B cells,and other cells; induces feverand catabolism
IL-2 T cell growth factor T cells (CD4+, CD8+), largegranular lymphocytes(natural killer, or NK, cells)
4q T cell proliferation, antitumor andantimicrobial effects
Factor Other Names Cell Source ChromosomeLocation
Function
IL-3 Multi–colony stimulating factor;mast cell growth factor
Activated T cells; large granularlymphocytes (NK cells)
5q23-q31 Proliferation of early hematopoieticcells
IL-4 B cell growth factor; T cellgrowth factor II; mast cellgrowth factor II
T cells 5q23-q31 Proliferation of B cells and T cells;enhances cytotoxic activities
IL-5 Eosinophil differentiation factor;eosinophil colony-stimulatingfactor
T cells 5q23.3-q32 Stimulates eosinophil formation;stimulates T cell and B cellfunctions
IL-6 B cell stimulatory factor II;hepatocyte stimulatory factor
Monocytes, tumor cells, B cellsand T cells, fibroblasts,endothelial cells
7p Stimulates and inhibits cellgrowth; promotes B celldifferentiation
IL-7 Lymphopoietin 1; pre–B cellgrowth factor
Lymphoid tissues and cell lines
8q12-q13 Growth factor for B cells and Tcells
IL-11 Plasmacytoma stimulatingfactor
Fibroblasts, trophoblasts, cancercell lines
19q13.3-q13.4 Stimulates proliferation of earlyhematopoietic cells; inducesacute-phase protein synthesis
Factor Other Names Cell Source ChromosomeLocation
Function
IL-12 Natural killer cell stimulatingfactor
Macrophages, B cells 5q31-q33;3p12-q13.2
Stimulates T cell expansion andinterferon-gamma; synergisticallypromotes early hematopoieticcell proliferation
LIF Leukemia inhibitory factor Monocytes and lymphocytes;stomal cells
22q Stimulates hematopoietic celldifferentiation
SCF Stem cell factor; kit ligand; steelfactor
Endothelial cells; hepatocytes
4q11-q20 Stimulates proliferation of earlyhematopoietic cells and mastcells
FLT-3ligand
fms-like tyrosine kinase 3;STK-1
T cells, stromal cells, andfibroblasts
19q13.3 Stimulates early hematopoietic celldifferentiation; increases blooddendrite cells
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