Granulocyte macrophage colonystimulating factor

GM-CSF is also known as CSF-a or pluripoietin-a. It is a 127 amino acid, single-chain, glycosylated polypeptide, exhibiting a molecular mass in the region of 22 kDa. It is produced by various cells (Table 10.5), and studies have indicated that its biological activities include:

• Proliferation/differentiation factor of haemopoietic progenitor cells, particularly those yielding neutrophils (a variety of granulocyte) and macrophages, but also eosinophils, erythrocytes and megakarycytes. In vivo studies also demonstrate this cytokine's ability to promote haemopoiesis.

• Activation of mature haemopoietic cells, resulting in:

• enhanced phagocytic activity;

• enhanced microbiocidal activity;

• augmented anti-tumour activity;

• enhanced leukocyte chemotaxis.

The intact GM-CSF receptor is a heterodimer, consisting of a low-affinity a-chain and a P-chain, which also forms part of the IL-3 and IL-5 receptors. (The P-chain alone does not bind GM-CSF.) The a-chain is an 80 kDa glycoprotein and exhibits only a short intracellular domain. The larger P-chain (130 kDa) displays a significant intracellular domain. Signal transduction involves the (tyrosine) phosphorylation of a number of cytoplasmic proteins (Figure 10.2).

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