AJP - Cell Physiology, Vol 262, Issue 4 C876-C881, Copyright © 1992 by American Physiological Society
Regulation of macrophage colony-stimulating factor in liver fat-storing cells by peptide growth factors
M. Pinzani, H. E. Abboud, L. Gesualdo and S. L. Abboud
Istituto di Clinica Medica II, University of Florence, Italy.
Macrophage colony-stimulating factor (M-CSF) selectively promotes
mononuclear phagocyte survival, proliferation, and differentiation. The
production of this factor within the liver may be necessary to support the
relatively long-term survival of circulating monocytes as they migrate into
tissues and differentiate into macrophages. We studied the constitutive
expression and the effects of platelet-derived growth factor (PDGF), basic
fibroblast growth factor (bFGF), and epidermal growth factor (EGF) on M-CSF
mRNA levels and secretion of M-CSF in murine liver fat-storing cells (FSC),
vascular pericytes likely involved in the development of liver fibrosis. By
Northern analysis, using a murine M-CSF cDNA, FSC constitutively express
two major transcripts of 4.4 and 2.2 kb, similar to those detected in mouse
L cells, used as a control. Exposure to 10 ng/ml PDGF or bFGF increased
M-CSF mRNA levels. Peak effects were observed at 3 and 6 h for PDGF and
bFGF, respectively, returning to baseline levels by 12 h. Under basal
conditions, detectable amounts of M-CSF, measured by radioimmunoassay, were
found in cell supernatants conditioned for 8 and 24 h. PDGF and bFGF
markedly stimulated the release of M-CSF as early as 8 h, an effect
persisting for at least 24 h. These findings suggest that liver FSC release
M-CSF upon stimulation by PDGF and bFGF and may contribute to the
activation of resident or infiltrating cells in inflammatory liver
diseases.
