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Control of fecal peritoneal infection in mice by colony-stimulating factors
J Barsig1, D S Bundschuh, T Hartung
1Faculty of Biology, University of Konstanz, Germany.
Abstract:
Granulocyte colony-stimulating factor (G-CSF) recruits and primes neutrophilic granulocytes. The role of endogenous and exogenous G-CSF was examined in a murine fecal peritoneal infection model characterized by rapid production of high levels of circulating G-CSF. Pretreatment with anti-murine G-CSF for 5 days reduced neutrophil counts by 50% and sensitized mice to sublethal peritonitis. There were more aerobic bacteria in livers of antiserum-pretreated animals but fewer neutrophils in peritoneal cavities. Pretreatment with 100 micrograms/kg recombinant murine G-CSF intravenously for 2 days raised neutrophil counts 5-fold and significantly protected animals against lethal peritonitis. A similar prophylactic administration of murine granulocyte-macrophage (GM)-CSF neither augmented leukocyte numbers nor protected infected mice. These results show a dissociation between the pharmacologic properties of GM-CSF and G-CSF and demonstrate the crucial role of endogenous G-CSF in controlling neutrophil-dependent defense against bacterial invasion in infection.
Insights
Granulocyte colony-stimulating factor (G-CSF) is crucial for controlling bacterial infections by boosting neutrophil numbers. Enhancing G-CSF levels protected mice against lethal peritonitis, highlighting its therapeutic potential.
Area of Science:
- Immunology
- Infectious Diseases
- Hematology
Background:
- Granulocyte colony-stimulating factor (G-CSF) is known to recruit and prime neutrophils.
- Bacterial peritonitis models rapidly produce high levels of circulating G-CSF.
Purpose of the Study:
- To investigate the role of endogenous and exogenous G-CSF in a murine model of fecal peritonitis.
- To compare the effects of G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF) in this infection model.
Main Methods:
- Mice were pretreated with anti-murine G-CSF or recombinant murine G-CSF.
- Mice were challenged with a fecal peritonitis model.
- Neutrophil counts, bacterial load in livers, and survival rates were assessed.
Main Results:
- G-CSF neutralization reduced neutrophil counts by 50% and increased susceptibility to peritonitis.
- Exogenous G-CSF administration increased neutrophil counts fivefold and conferred significant protection against lethal peritonitis.
- GM-CSF administration did not alter leukocyte numbers or protect against infection.
Conclusions:
- Endogenous G-CSF plays a critical role in neutrophil-dependent defense against bacterial invasion.
- G-CSF demonstrates significant therapeutic potential in managing bacterial peritonitis.
- G-CSF and GM-CSF exhibit distinct pharmacologic properties and in vivo effects during infection.