Lipopolysaccharide induces synthesis of mouse colony-stimulating factor-1 in vivo.
CSF-1 is a hemopoietic growth factor that regulates the survival, proliferation, and differentiation of mononuclear phagocytes, cells that are critical in the inflammatory response. In the case of Gram-negative infection, LPS plays an important role by inducing several cell types to produce the proinflammatory cytokines, IL-1, IL-6, and TNF-alpha. In this study, we examined the effects of i.p. administration of LPS on CSF-1 expression in the mouse. Two- to sevenfold increases in the CSF-1 concentrations determined by RIA were evident within hours of LPS administration in serum, liver, kidney, lung, spleen, brain, intestine, and heart. While alterations in the CSF-1 receptor-mediated clearance of CSF-1 appeared not to account for the increased growth factor concentrations in LPS-treated animals, there was an early LPS-induced reduction of splenic [125I]CSF-1 uptake consistent with tissue-specific down-modulation of CSF-1 receptors. The results of Northern analysis revealed increased expression of a CSF-1 mRNA species in liver, lung, kidney, spleen, intestine, and heart following LPS treatment, demonstrating that increased synthesis was responsible for the increased tissue CSF-1 concentrations. The increased expression and synthesis of CSF-1 in response to LPS may be essential for mobilizing and activating mononuclear phagocytes in the inflammatory response.
Roth
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P
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Bartocci
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A
Stanley
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ER
D000818:Animals; D005260:Female; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*
D008070:Lipopolysaccharides; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor