HEMATOPOIESIS THIRD YEAR MEDICAL STUDENT

OUTLINEINTRODUCTION

HAEMATOPOIETIC STEM AND PROGENITOR CELLS

ADHESION MOLECULES

HAEMATOPOIETIC GROWTH FACTORS

INTRODUCTIONHSCs arise in york sac and the intraembryonic aorta/gonad/mesoneophros regionLong-term reconstituting hematopoietic stem cells (LTR-HSCs) are cells capable of long-term reconstitution of myelopoiesis and lymphopoiesis

HAEMATOPOIETIC STEM AND PROGENITOR CELLSHaemopoietic stem cells- self-renewal and differentiationThe earlier progenitor cells are multipotent The marrow contains a stromal matrix that provide the correct microenvironment for stem cell growth

Progenitor CellsErythroid colony-forming cells entire process requires about 2 wks in vitro

Granulocyte and macrophage colony-forming cells 12-14 days is required for full maturation

Megakaryocyte colony-forming cells 7-10 days is required

The granulocyte monocyte macrophage differentiation pathway

The erythroid differentiation pathway

The production of erythropoietin

Role of cytokines in megakaryocytopoiesis

ADHESION MOLECULESMediate the attachment of various body cells to each other and extracellular matrix

Include 6 groups according to the molecular structure3 main groups- immunoglobulin, selectins and integrins3 smaller groups- cadherins, syndecams, ADAMS

ADHESION MOLECULESImmuglobulin superfamilyAntigen receptor- T-cell receptor, IgsGrowth factors receptors

Selectins- leucocyte and platelet adhesionto endothelium during inflammation or coagulation

Integrins- important in immune function, tissue repair and platelet aggregation

Adhesion molecules and growth factors

Stromal cells and extracellular matrix

HAEMATOPOIETIC GROWTH FACTORSProduced by stromal cells of the microenvironment and the haemopoietic cells themselvesFor example; colony-stimulating factor, interleukins (ILs), the kidneys (erythropoietin) or liver (thrombopoietin)

HAEMATOPOIETIC GROWTH FACTORSAre glycoprotiens involved in the self-renewal of stem cells and the proliferation and differentiation of lineage-committed progenitor cells

HAEMATOPOIETIC GROWTH FACTORSThe sources of the CSFs are marrow stromal cells (fibroblast and endothelial cells), lymphocytes and macrophages

Types of Hematopoietic Growth factorsLineage-specific hematopoietic growth factors: G-CSF, M-CSF, IL-5, TPO and EPO

Multilineage hematopoietic growth factors: IL-3 and GM-CSF

Early-acting hematopoietic growth factors: SCF and FL

Synergistic factors: IL-1, IL6 and IL-11

Negative regulator of hematopoietic growth factors: transforming growth factors

HAEMATOPOIETIC GROWTH FACTORSIL-3 and GM-CSF are required throughout haemopoiesis, acting on pluripotent and early progenitor cells

required for self-renewal and differentiaiton

HAEMATOPOIETIC GROWTH FACTORSG-CSF, M-CSF,, IL-5, thrombopoietin and erythropoietin act on more mature cells of a specific lineage

They also act synergistically with other growth factor on early cells

Questions

HAEMATOPOIETIC GROWTH FACTORSErythropoietin

Derived from kidney and liver

Secreted in response to anoxia caused for example by anemia or high attitude

Stimulated erythropoiesis at the committed CFUE stage, BFUE progenitors, later cells up to reticulocyte stage

HAEMATOPOIETIC GROWTH FACTORSThrombopoietin

Stimulated survival and proliferation of haemopoietic stem and megakaryocyte colony-forming cells

Stimulated formation of megakaryocytes, including megakaryocyte maturation and release of platelet into the blood

HAEMATOPOIETIC GROWTH FACTORSHas an elimination half-life of 30 hoursBeing with erythropoietin, stimulated growth of erythroid progenitor cells

Colony-Stimulating FactorsGM-SCF

Its ability to stimulate colonies of neutrophils and macrophagess

Acts on many cell types including early multipotential sttem cells, megakaryocyte, eosinophil, erythroid and mature neutrophils and macrophages

Stimulates of cytotoxic and phagocyte activity against bacteria, yeast, and parasites

May also raise the platelet count and possibly the reticulocyte level

Colony-Stimulating FactorsG-CSF

Stimulate predominantly neutrophil colony formation

Cytokines active on lymphohematopoiesis stem and progenitor cells

Interleukin-1Defined as a macrophage product inducing IL-2 receptor expression on T lymphocytes

Activation of cells involved in early stages of hematopoiesis The inflammatory responseWound healingActivates lymphocytes, neutrophils and macrophages and NK cellsActs as endogenous pyrogensInduces proliferation of fibroblasts, epithelial and endothelial cells

Interleukin-2Is T-cell growth factor

Promotes the proliferation of T-lymphocytes, B-lymphocytes and monocytes

Promotes cytotoxic function by stimulating the proliferation and activity of NK cells

May inhibit both granulocyte-macrophage colony formation and erythropoiesis

Interleukin-5Knows as eosinophil differentiation factor

Support the proliferation, maturation and function of eosinophils

Interleukin-6Has a wide effects in hemopoiesis

Interacts synergistically with other growth factors to stimulate myeloid proliferation

Is a major factor in the immune response and inflammation and act as acute phase protein

Stimulates granulocyte-macrophage and megakaryocyte colony formation

Interleukin-6

Other cytokinesFlt-3 ligand acts on relatively primitive progenitor stem cells showing synergies with G-CSF, GM-CSF, M-CSF, IL-3 and SCF