Function and Regulation of the Hematopoietic Bone Marrow

Function and regulation of the hematopoietic bone marrowOMOH has an important production role because this system must produce 10 1 ê 3 blood cells perday to compensate for losses and this continues. Cells hematopoietic cells are divided into 3compartments of unequal importance: pluripotent stem cells Progenitors already involved in certainlineages/The precursors.OThe pluripotent cell is dormant but can also enter a cycle. It can differentiate to give either alymphoid progenitor or a mixed progenitor. These are elements which are not morphologicallyidentifiable: they are not precursors but progenitors. For progenitors we use CFU for colonyforming units: these are cells capable of forming colonies in cell culture. This element gives clumpsof cells in culture which can then differentiate according to the cytokines that can be add to themedium either towards the erythroblastic or megakaryocytic, granular lineage or monocytic, this iswhy we say CFU: G for granular, E for erythrocyte, N for megakaryocytic and M for monocytic SoCFU G, E, N. M: a mixed progenitor. From this mixed progenitor we can have the erythroblasticlineage, BFU for burst forming units which is another type of colony. From this mixed progenitorwe have the possibility of having a megakaryocytic progenitor or a progenitor that is still mixedwhich makes both granulocytes and monocytes.The progenitors for eosinophils and basophils are different from that which will give rise to theprogenitor for either the granular (the neutrophil) or the monocytes. The eosinophil lineage is verysensitive to Interleukin 5 and basophil to interleukin 1.OMOH has a role in the release of cellular elements that we dislike in Diabase. This releasegenerally only concerns mature elements It's a trans passage endothelial cell and generally the porediameter of sinusoidal capillaries is less than the size of the elements and there are only mature cellswhich have the capacity to deform and therefore to be able to pass through these pores. The orificesare not permanent and the elements which want to pass must have the possibility of migrating anddeforming Diabase is regulated by erythropoietin which will promote the passage of reticulocytesinto the bloodOWe can also have bacterial endotoxins which can modify the diameter of the pores: for examplein cases of pneumococcal pneumonia which are severe bacterial infections, we can have immatureelements of the granular lineage therefore for example metamyelocytes or neutrophil myelocytes inthe circulating blood because the MOH is stimulated in its production and at this time we havereleased polynuclear neutrophils, we have a large production and some immature elements canpass. There can be passage of other immature elements in pathological circumstances: for example ifthe medullary cavities are occupied by things other than MOH, it could be an invasion by malignantcells/cancer and at this moment these cells take the place of the MOH and push out the immatureelements.OMOH has a role in uptake and phagocytosis since there are numerous macrophages in the MOH.It may be an uptake of bacteria and phagocytosis of senescent erythrocytes and macrophages sendcytoplasmic extensions through the endothelial cells. -Regulation of hematopoiesis:The important thing is the economy of cell strains. We have our totipotent stem cell which isdormant and this cell has the capacity to self-renew without necessarily triggering a phenomenon ofcellular differentiation and At this point the stem cells can once again be dormant Either the stemcell will engage in a path of differentiation, the fact that it remains dormant for example, TGF betawill promote maintenance in a dormant or quiescent state by a weak response to growth factors andalso due tone increase in the P27 protein which inhibits cyclin dependent kinase and therefore stopsthe cell cycle. If the concentration of TGF beta 1 decreases or we give anti-TGF, at that moment wehave a drop in P27, an entry into the cycle and the expressionession of receptors for example for thestem cell factor, receptors for interleukin 8, for other growth factors, a decrease in CD34. This doesthat the cell becomes activated Not only is there a modification of the receptors for growth factorsbut there are also modifications for molecules which allow adhesions between cells: for example wehave transmembrane receptors called NOTCH and JAG. These molecules are members of asuperfamily of receptors including evolution JAG molecules can be carried by stromal cellstherefore fibroblasts and NOTCH molecules by hematopoietic cells and if we have high expressionlevels of these receptors we now have dent of the stem cells in an undifferentiated state otherwisewe have modifications of the transcription factors and at this time the cells start to cycle.