Growth factors - Pharmaceutical Biotechnology: Concepts and Aapplications - page 272

derived from the same gene and share common C and N termini. The largest consists of 522
amino acids, with the 406 and 224 amino acid forms lacking different lengths of the internal
sequence of the 522 form. The molecular masses of these mature M-CSFs range from 45 to
90 kDa.
The biologically active form of M-CSF is a homodimer (two identical subunits). These
homodimers can exist as integral cell surface proteins, or may be released from their producer cell
by proteolytic cleavage, thus yielding the soluble cytokine. The M-CSF receptor is a single-chain,
heavily glycosylated, polypeptide of molecular mass 150 kDa.

10.2.4 Granulocyte macrophage colony-stimulating factor

G M - C S F i s a l s o k n ow n a s C S F - α or pluripoietin-α. 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 yield-

ing 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.

-chain,
which also forms part of the IL-3 and IL-5 receptors. (The β-chain alone does not bind GM-CSF.)
The

The intact GM-CSF receptor is a heterodimer, consisting of a low-affi nity α -chain and a β

-chain is an 80 kDa glycoprotein and exhibits only a short intracellular domain. The larger
β-chain (130 kDa) displays a signifi cant intracellular domain. Signal transduction involves the
(tyrosine) phosphorylation of a number of cytoplasmic proteins (Figure 10.2).

α

10.2.5 Clinical application of colony-stimulating factors

Several CSF preparations have gained regulatory approval (Table 10.2). G-CSF and GM-CSF
have proven useful in the treatment of neutropenia. All three CSF types are (or are likely to be)
useful also in the treatment of infectious diseases, some forms of cancer and the management of
bone marrow transplants, as they stimulate the differentiation/activation of white blood cell types
most affected by such conditions.