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Macrophages as origin of factor increasing monocytopoiesis
W Sluiter1, E Hulsing-Hesselink, I Elzenga-Claasen
1Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Abstract:
Earlier investigations had indicated that the factor increasing monocytopoiesis (FIM), present in the serum of mice and rabbits during the onset of an inflammatory response, is released by cells of the inflammatory exudate. The present study was performed to determine which cells produce and secrete this factor and to establish the kinetics of its production and secretion. FIM was assayed in vivo by intravenous injection of samples into untreated mice and monitoring the course of the number of blood monocytes in the recipients. FIM was assayed in vitro by adding samples to cultures of the macrophage cell line PU5 and determining the rate of proliferation of the cells. The results show that only macrophages contain and synthesize FIM. This factor is secreted upon exposure to a phagocytic stimulus, and after the release of preformed FIM, macrophages secrete newly synthesized FIM. Granulocytes and lymphocytes neither contain nor secrete FIM. The characteristics of FIM derived from macrophages are in all aspects similar to those of FIM in serum. Macrophage-derived FIM is a protein with a molecular weight between 10 and 25 X 10(3), its activity is cell-lineage specific and dose dependent, and it stimulates monocyte production in the bone marrow. Macrophage-derived FIM is not identical to either CSF-1 or IL-1, and has no chemotactic activity. Taken together, the present results show that FIM occurring in serum during an inflammatory response originates from macrophages at the site of the inflammation. In this way the macrophages themselves regulate the supply of circulating blood monocytes that can migrate to the site of injury when needed.
Insights
Macrophages produce and secrete the factor increasing monocytopoiesis (FIM) during inflammation. This protein regulates circulating blood monocyte supply to injury sites.
Area of Science:
- Immunology
- Cell Biology
Background:
- Previous studies suggested inflammatory exudate cells release the factor increasing monocytopoiesis (FIM).
- The specific cell types responsible for FIM production and secretion remained unidentified.
Purpose of the Study:
- To identify the cells responsible for producing and secreting FIM.
- To elucidate the kinetics of FIM production and secretion.
Main Methods:
- In vivo assay: Intravenous injection of samples into mice to monitor blood monocyte counts.
- In vitro assay: Culturing the macrophage cell line PU5 with samples to assess cell proliferation.
Main Results:
- Macrophages were identified as the sole source of FIM synthesis and content.
- FIM secretion is triggered by phagocytic stimuli, involving both preformed and newly synthesized factor.
- Granulocytes and lymphocytes do not contain or secrete FIM.
- Macrophage-derived FIM exhibits characteristics similar to serum FIM, including molecular weight (10-25 kDa), cell-lineage specificity, dose dependency, and bone marrow monocyte stimulation.
- Macrophage-derived FIM is distinct from CSF-1 and IL-1 and lacks chemotactic activity.
Conclusions:
- Macrophages at inflammatory sites are the origin of serum FIM during inflammation.
- Macrophages actively regulate the circulating blood monocyte pool, ensuring supply to sites of injury.