Production of colony-stimulating factors (CSFs) during infection: separate determinations of macrophage-, granulocyte-, granulocyte-macrophage-, and multi-CSFs

Abstract

After infection of mice with Listeria monocytogenes, elevated levels of colony-stimulating factors (CSFs) in the serum were quantitated by six different assays: ability to stimulate colony formation, the proliferation of 2 suspension of bone marrow cells (both measuring total colony-stimulating activity), a radioimmunoassay for macrophage-CSF (CSF-1), the WEHI-3B differentiation assay for granulocyte-CSF, and proliferation of 32D-cl-3 and FDC-Pl cell lines (specific for multi-CSF and either multior granulocyte-macrophage-CSFs, respectively). The great bulk of serum colony-stimulating activity represented macrophageand granulocyte-CSFs, with small but measurable amounts of granulocyte-macrophage-CSF. The degree of elevation of serum CSF depended on the infecting dose used and the numbers of bacteria growing in the spleens and livers of the two mouse strains compared, i.e., L. monocytogenes-resistant C57BL/10 and susceptible BALB/cJ. The increase in serum CSFs occurred before the peak in bone marrow granulocyte-macrophage progenitors and before the reduction in bacterial numbers which follows the onset of specific cell-mediated immunity.

Functional deficiencies of peritoneal cells from gene-targeted mice lacking G-CSF or GM-CSF

“…Macrophages from transgenic mice overexpressing GM-CSF showed increased phagocytosis of bacteria in vitro [3]. It is consistent with a role for CSFs in protection against infection that the levels of expression are increased after infection [4].…”

Demystifying the development of dendritic cell subtypes, a little

“…First, it is sometimes underrecognized that GM-CSF levels are 'below detection' in steady-state mice and in healthy humans [192][193][194][195][196][197] and so may not contribute to significant steady-state in vivo DC generation from monocytes. There are three possibilities that could count for this discrepancy between the presence of DCs in vivo and levels of GM-CSF; GM-CSF levels, although low, are still functional; there are factors in vivo that substitute for GM-CSF to generate DCs; steady-state DCs may actually be a distinct pathway from those that are monocyte derived.…”

Innate defenses in the liver during Listeria infection

“…One critical stimulus for infiltration of Mac1 + cells into the liver is macrophage colony-stimulating factor (M-CSF). M-CSF expression in the liver is rapidly induced in a dose-dependent manner during Listeria infection (14,(82)(83)(84)(85). In vivo treatment with either anti-M-CSF or anti-M-CSF receptor mAb reduces Mac1 + cell infiltration into livers and increases the number of listeriae associated with either hepatocyte or leukocyte populations.…”