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Lipopolysaccharide induces synthesis of mouse colony-stimulating factor-1 in vivo
P Roth1, A Bartocci, E R Stanley
1Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Abstract:
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.
Insights
Lipopolysaccharide (LPS) administration significantly increases colony-stimulating factor-1 (CSF-1) levels throughout the mouse body. This rise in CSF-1 is due to increased gene expression and synthesis, crucial for immune cell activation during inflammation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Colony-stimulating factor-1 (CSF-1) is a key hemopoietic growth factor regulating mononuclear phagocytes, vital for inflammatory responses.
- Lipopolysaccharide (LPS) from Gram-negative bacteria induces pro-inflammatory cytokines like IL-1, IL-6, and TNF-alpha.
Purpose of the Study:
- To investigate the impact of intraperitoneal (i.p.) LPS administration on CSF-1 expression in mice.
- To determine the mechanisms behind increased CSF-1 concentrations following LPS exposure.
Main Methods:
- Radioimmunoassay (RIA) to measure CSF-1 concentrations in various tissues and serum.
- Assessment of CSF-1 receptor-mediated clearance and splenic uptake of [125I]CSF-1.
- Northern blot analysis to evaluate CSF-1 mRNA expression in different organs.
Main Results:
- LPS administration led to a rapid, two- to sevenfold increase in CSF-1 concentrations across serum, liver, kidney, lung, spleen, brain, intestine, and heart.
- Increased CSF-1 levels were attributed to enhanced gene expression and synthesis, as evidenced by increased CSF-1 mRNA.
- A transient decrease in splenic [125I]CSF-1 uptake suggested tissue-specific down-modulation of CSF-1 receptors.
Conclusions:
- LPS significantly upregulates CSF-1 expression and synthesis in multiple tissues.
- This LPS-induced increase in CSF-1 is likely essential for mobilizing and activating mononuclear phagocytes during inflammatory responses.