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Bone marrow cell response following induction of acute inflammation in different strains of mice
G N Pozzulo1, E Skamene, F Gervais
1McGill Center for the Study of Host Resistance, Montreal General Hospital Research Institute, Quebec, Canada.
Abstract:
The magnitude of the macrophage inflammatory response differs among inbred mouse strains. Mice of the A/J strain respond poorly to sterile inflammatory stimuli while those of the C57BL/6 strain show a strong response. Inflammatory macrophages found at the site of inflammation are the product of bone marrow (BM) myeloid stem cells. Mice of the A/J strain were found to have half the number of BM nucleated cells per femur than those of the C57BL/6 strain. The lower BM cellularity may be one reason for the poor macrophage inflammatory response observed in A/J mouse strain. Using A x B/B x A recombinant inbred mouse strains, we determined that the number of nucleated cells per femur found in normal mice was not a determining factor of the magnitude of the macrophage inflammatory response. One additional explanation for the poor macrophage inflammatory response in mice of the A/J strain is their deficiency in the C5 component of complement. Using a C5-sufficient A/J.C5 congenic strain, we have previously shown that the presence of C5 on the A/J background improved their inflammatory response. We compared A/J and A/J.C5 mouse strains to determine whether or not C5 had an impact on the BM cell response to inflammatory stimulus. The presence of C5 on the A/J background could contribute to the improvement of the inflammatory response in mice of the A/J.C5 strain by inducing a greater number of nucleated cells to exit the BM compartment early following induction of inflammation.
Insights
The C5 complement component enhances macrophage inflammatory responses in A/J mice by increasing bone marrow cell release. This finding is crucial for understanding immune differences between mouse strains and potential therapeutic targets.
Area of Science:
- Immunology
- Inflammation Research
Background:
- Macrophage inflammatory responses vary significantly across inbred mouse strains, with A/J mice exhibiting a poor response compared to C57BL/6 mice.
- Bone marrow (BM) myeloid stem cells generate inflammatory macrophages, and A/J mice have lower BM cellularity, potentially explaining their diminished response.
Purpose of the Study:
- To investigate the impact of the C5 complement component on the bone marrow cell response to inflammatory stimuli in A/J mice.
- To determine if C5 influences the number of nucleated cells released from the bone marrow during inflammation.
Main Methods:
- Comparison of A/J and C5-sufficient A/J.C5 congenic mouse strains.
- Assessment of bone marrow cellularity and cell release following inflammatory stimulus induction.
Main Results:
- The number of nucleated cells per femur in normal mice was not a determining factor for the magnitude of the macrophage inflammatory response.
- The presence of C5 on the A/J background in the A/J.C5 strain was associated with an improved inflammatory response.
- C5 may enhance the inflammatory response by promoting earlier exit of nucleated cells from the bone marrow.
Conclusions:
- Complement component C5 plays a significant role in modulating the macrophage inflammatory response in A/J mice.
- C5 deficiency contributes to the poor inflammatory response in A/J mice.
- The mechanism involves C5 potentially increasing nucleated cell egress from the bone marrow during inflammation.