The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor

Details

Serval ID
serval:BIB_ECD03FF95A59
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor
Journal
Journal of Experimental Medicine
Author(s)
Calandra  T., Bernhagen  J., Mitchell  R. A., Bucala  R.
ISSN
0022-1007 (Print)
Publication state
Published
Issued date
06/1994
Volume
179
Number
6
Pages
1895-902
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jun 1
Abstract
For over 25 years, the cytokine known as macrophage migration inhibitory factor (MIF) has been considered to be a product of activated T lymphocytes. We recently identified the murine homolog of human MIF as a protein secreted by the pituitary in response to endotoxin administration. In the course of these studies, we also detected MIF in acute sera obtained from endotoxin-treated, T cell-deficient (nude), and hypophysectomized mice, suggesting that still more cell types produce MIF. Here, we report that cells of the monocyte/macrophage lineage are an important source of MIF in vitro and in vivo. We observed high levels of both preformed MIF protein and MIF mRNA in resting, nonstimulated cells. In the murine macrophage cell line RAW 264.7, MIF secretion was induced by as little as 10 pg/ml of lipopolysaccharide (LPS), peaked at 1 ng/ml, and was undetectable at LPS concentrations > 1 microgram/ml. A similar stimulation profile was observed in LPS-treated peritoneal macrophages; however, higher LPS concentrations were necessary to induce peak MIF production unless cells had been preincubated with interferon gamma (IFN-gamma). In RAW 264.7 macrophages, MIF secretion also was induced by tumor necrosis factor alpha (TNF-alpha) and IFN-gamma, but not by interleukins 1 beta or 6. Of note, MIF-stimulated macrophages were observed to secrete bioactive TNF-alpha. Although previously overlooked, the macrophage is both an important source and an important target of MIF in vivo. The activation of both central (pituitary) and peripheral (macrophage) sources of MIF production by inflammatory stimuli provides further evidence for the critical role of this cytokine in the systemic response to tissue invasion.
Keywords
Animals Base Sequence Blotting, Western Cell Line DNA Primers Female Humans Hypophysectomy Introns Kinetics Lipopolysaccharides/pharmacology Macrophage Migration-Inhibitory Factors/analysis/*biosynthesis/pharmacology Macrophages/drug effects/*metabolism Mice Mice, Inbred BALB C Mice, Nude Molecular Sequence Data Organ Specificity Polymerase Chain Reaction Recombinant Proteins/pharmacology T-Lymphocytes/metabolism Tumor Necrosis Factor-alpha/biosynthesis
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 14:28
Last modification date
20/08/2019 17:14
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