The nature and action of granulocyte-macrophage colony stimulating factors

Abstract

Granulocyte-macrophage colony stimulating factor (GM-CSF) stimulates the in vitro proliferation and differentiation of granulocytic and macrophage cells. This regulator is now known to act at other levels of hemopoietic regulation. The heterogeneity of GM-CSFs is not only related to the tissue of origin and the in vitro production method, but also to functional subclasses of the molecule that have distinct biologic specificities. Most adult mouse organs produce GM-CSF (mol wt 23,000), but a macrophage (M)-CSF has been detected in fetal conditioned medium (CM) and isolated from L-cell CM. Murine endotoxin serum appears to contain a M-CSF, GM-CSF, and G-CSF, the last of which cofractionates with a differentiation factor active on leukemic cells. Human GM-CSFs, G-CSF, and EO-CSFs active on human cells have been detected in a variety of CM, but as yet none have been purified. Again, there are subclasses of progenitor cells that respond to particular forms of human active CSFs. GM-CSF isolated from mouse lung CM stimulates multipotential progenitor cells, the initial proliferatin of progenitors in the erythroid, eosinophil, and megakaryocyte series, as well as mature cells in the GM series. While GM-CSF is also able to stimulate the differentiation of myeloid leukemic cells, other factors appear to be more potent in this respect. Information on the regulation of GM-CSF production, on the modulators of its action on specific target cells, and on its role in vivo will be required before the physiologic function of this molecule can be properly assessed.

Requirement for macrophages or for macrophage‐ or T cell‐derived factors in the mitogenic stimulation of murine B lymphocytes by lipopolysaccharides

“…with LPS (SO pg) and AE (300 pg) followed by in vitro stimulation with Con A (5 pgiml) for 24 h. Con A-activated T91-4 and Tll-14 hybridoma supernatants were prepared as rat Con A supernatants (see above), but without further purification. They contained no detectable quantities of T cell growth factor (IL2) [47] or CSF [48] but had BRF and BMF activity [25]. Conditioned media were used in the presence of 5 mM a-methylmannoside (Sigma Chemical Co., St. Louis, MO).…”

Purification and characterization of human granulocyte colony-stimulating factor (G-CSF).

“…By clonal assay of bone marrow cells using the semi-solid culture system, it has been shown that neutrophilic granulocytes originate from multipotent stem cells and that the proliferation and differentiation in vitro of the progenitor cells of the granulocytemacrophage lineage are regulated by a family of glycoproteins (Sachs, 1970;Metcalf, 1977;Burgess and Metcalf, 1980). These molecules are generally called colonystimulating factors (CSFs) or macrophage and granulocyte inducers (MGIs) (Landau and Sachs, 1971;Sachs, 1978Sachs, , 1980; on the basis of morphology of the colonies stimulated, these factors are classified into at least four biochemically distinct subtypes, that is, multi-, granulocyte-macrophage (GM)-, macrophage (M)-and granulocyte (G)-CSFs (Metcalf, 1985;Sachs, 1985).…”

The chromosomal gene structure and two mRNAs for human granulocyte colony-stimulating factor.

“…The proliferation and differentiation of the progenitor cells for granulocytes and macrophages are regulated by a family of proteins called colony-stimulating factors (CSF) (Burgess and Metcalf, 1980;Metcalf, 1985). In the murine system, four CSFs have been well characterized; granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), macrophage CSF (M-CSF) and interleukin 3 (IL-3) (Metcalf, 1985).…”