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Differences in the response of inbred mouse strains to the factor increasing monocytopoiesis
Abstract:
Previous studies have shown that monocyte production during an inflammatory response is controlled by the factor increasing monocytopoiesis (FIM), secreted by macrophages at the site of inflammation. The inflammatory reaction to latex particles and a saline-soluble extract of Listeria monocytogenes (SEL), expressed as the number of monocytes in the circulation and of macrophages at the site of inflammation, was about twice as strong in C57BL/10 mice compared with CBA mice. This raised the question as to the mechanism underlying these differences. One possibility might be that these mouse strains differ with respect to the production of FIM, but this cannot be the case because the maximum levels of FIM activity in the serum of both C57BL/10 and CBA mice given latex or SEL intraperitoneally were almost the same; however, the courses of FIM activity in the two strains after intraperitoneal latex were not exactly synchronous. Another possibility is that the sensitivity of monocyte precursor cells for FIM differs. Evidence for the latter was provided by the finding that the intravenous injection of sera with FIM activity obtained from C57BL/10 and from CBA mice into the C57BL/10 mice evoked monocytosis, whereas CBA mice did not respond to these sera. Earlier studies showed that an increase of monocytes after the injection of serum containing FIM reflects increased monocyte production. Taken together, the results of the present study demonstrate that one of the mechanisms underlying the genetic control of the inflammatory response is, rather than enhanced FIM synthesis, the ability of monocyte precursors in the bone marrow to respond to FIM by increased monocyte production.
Insights
Genetic differences in inflammatory responses stem from how well monocyte precursors in the bone marrow respond to the factor increasing monocytopoiesis (FIM), not from differences in FIM production.
Area of Science:
- Immunology
- Hematology
Background:
- Monocyte production during inflammation is regulated by factor increasing monocytopoiesis (FIM), secreted by macrophages.
- Significant strain-dependent differences exist in inflammatory responses, with C57BL/10 mice exhibiting stronger reactions than CBA mice.
Purpose of the Study:
- To investigate the underlying mechanisms responsible for observed genetic differences in inflammatory responses between mouse strains.
- To determine whether differences in FIM production or monocyte precursor sensitivity account for varying inflammatory reactions.
Main Methods:
- Comparing inflammatory responses (monocyte and macrophage counts) in C57BL/10 and CBA mice after stimulation with latex particles and Listeria extract.
- Measuring serum FIM activity in both mouse strains following inflammatory stimuli.
- Assessing monocyte precursor cell responsiveness by injecting sera with FIM activity into different mouse strains.
Main Results:
- Both C57BL/10 and CBA mice showed similar peak serum FIM levels, indicating comparable FIM production.
- C57BL/10 mice exhibited a stronger inflammatory response than CBA mice.
- Monocyte precursors in C57BL/10 mice responded to FIM by increasing monocyte production, while CBA mice did not show a similar response.
Conclusions:
- Genetic control of inflammatory response intensity is primarily mediated by the differential responsiveness of bone marrow monocyte precursors to FIM.
- Enhanced FIM synthesis is not the primary mechanism driving the observed strain-specific differences in inflammatory responses.