LEUKAEMIA INHIBITORY FACTOR (LIF)<\/p>\n

LIF is an additional haemopoietic growth factor. It is also known as HILDA (human interleukin for DA cells) and hepatocyte stimulatory factor III. It is produced by a range of cell types, including T cells, liver cells and fibroblasts. LIF is a 180 amino acid, heavily glycosylated, 45 kDa protein. It affects both haemopoietic and non haemopoietic tissue, often acting in synergy with other cytokines, particularly IL-3. It stimulates the differentiation of macrophages and promotes enhanced platelet formation. It also prompts synthesis of acute phase proteins by the liver and promotes increased bone resorption. The greatest concentrations of LIF receptors are associated with monocytes, embryonic stem cells, liver cells and the placenta. The receptor complex is composed of two transmembrane glycoproteins: the 190kDa LIFRa-chain which displays affinity for LIF, and a b-chain (gp130), which also forms part of the IL-6 receptor.<\/p>\n

ERYTHROPOIETIN (EPO)<\/p>\n

EPO is an atypical cytokine in that it acts as a true (endocrine) hormone and is not synthesized by any type of white blood cell. It is encoded by a single copy gene, located on (human) chromosome 7. The gene consists of four introns and five exons. The mature EPO gene product contains 166 amino acids and exhibits a molecular mass in the region of 36 kDa EPO is a glycoprotein, almost 40% of which is carbohydrate. Three N-linked and one O-linked glycosylation site are evident. The O linked carbohydrate moiety apears to play no essential role in the (in vitro or in vivo) biological activity of EPO. Interestingly, removal of the N-linked sugars, while having little effect on EPO\u2019s in vitro activity, destroys its in vivo activity. The sugar components of EPO are likely to contribute to the molecule\u2019s:\u00a0solubility;\u00a0cellular processing and secretion;\u00a0in vivo metabolism.\u00a0EPO stimulates erythropoiesis by:<\/p>\n

\n
1. increasing the number of committed cells capable of differentiating into erythrocytes;<\/li>\n
2. accelerating the rate of differentiation of such precursors;<\/li>\n
3. increasing the rate of haemoglobin synthesis in developing cells.<\/li>\n<\/ol>\n

   THROMBOPOIETIN<\/p>\n

   Thrombopoietin (TPO) is the haemopoietic growth factor now shown to be the primary physiological regulator of platelet production. Although its existence had been inferred for several decades, its purification from blood proved an almost impossible task, due to its low production levels and the availability of only an extremely cumbersome TPO bioassay. Its existence was finally proved in the mid-1990s when thrombopoietin cDNA was cloned. This molecule is likely to represent an important future therapeutic agent in combating depressed plasma platelet levels, although this remains to be proved by clinical trials. A number of disorders have been identified that are primarily caused by the presence of abnormal platelet levels in the blood. Thrombocythaemia is a disease characterized by abnormal megakaryocyte proliferation, leading to elevated blood platelet levels. In many instances, this results in an elevated risk of spontaneous clot formation within blood vessels. In other instances, the platelets produced are defective, which can increase the risk of spontaneous or prolonged bleeding events.<\/p>\n

   Reference:<\/p>\n

   Walsh, G. (2013). Biopharmaceuticals: biochemistry and biotechnology. John Wiley & Sons.<\/p>\n","protected":false},"excerpt":{"rendered":"

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