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Updated: Aug 28, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Bacterial translocation and lipopolysaccharide-induced mortality in genetically macrophage-deficient op/op mice
B A Feltis1, R P Jechorek, S L Erlandsen
1Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis 55455, USA.
Abstract:
Genetically macrophage-deficient op/op mice have a total absence of macrophage colony-stimulating factor (also known as colony-stimulating factor 1 or CSF-1), and therefore an absence of a population of macrophages dependent on CSF-1. op/op mice also have profound secondary deficiencies in certain cytokines secreted by this macrophage population, such as tumor necrosis factor, interleukin-1, and granulocyte colony-stimulating factor. In the present study, op/op mice were used to clarify the role of the macrophage in two clinical processes: (a) bacterial translocation in response to antibiotic-induced intestinal overgrowth, and (b) endotoxin-induced bacterial translocation, morbidity, and mortality. The results were unexpected, in that bacterial translocation and endotoxin-induced morbidity and mortality were similar in op/op mice and their functionally normal littermates. These data indicated either that a specific macrophage population and its cytokines (including tumor necrosis factor and interleukin 1) might not play pivotal roles in the pathogenesis of bacterial translocation and endotoxin-induced septic shock, or alternatively, as yet unknown redundancies in vivo might compensate for the genetic deficiencies associated with the op/op mutation.
Insights
Macrophage-deficient mice showed no difference in bacterial translocation or endotoxin shock compared to normal mice. This suggests macrophages may not be critical in these conditions, possibly due to compensatory mechanisms.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Macrophage colony-stimulating factor (CSF-1) is crucial for macrophage development.
- op/op mice lack CSF-1 and associated macrophages, impacting cytokine production (e.g., TNF, IL-1).
- Macrophages play a role in host defense and inflammatory responses.
Purpose of the Study:
- To investigate the role of macrophages in bacterial translocation.
- To determine the impact of macrophage deficiency on endotoxin-induced septic shock.
Main Methods:
- Utilized genetically macrophage-deficient op/op mice and their normal littermates.
- Studied bacterial translocation following antibiotic-induced intestinal overgrowth.
- Assessed bacterial translocation, morbidity, and mortality after endotoxin challenge.
Main Results:
- Bacterial translocation was similar in op/op mice and normal littermates under both conditions.
- Endotoxin-induced morbidity and mortality were comparable between op/op mice and controls.
- Macrophage deficiency did not significantly alter the outcomes studied.
Conclusions:
- The specific CSF-1-dependent macrophage population and its cytokines may not be essential for preventing bacterial translocation.
- These findings challenge the presumed pivotal role of macrophages and specific cytokines in endotoxin shock pathogenesis.
- In vivo biological redundancies might compensate for the genetic absence of macrophages in op/op mice.
