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Macrophage suppression of granulocyte and macrophage growth following burn wound infection
1Shock Trauma Institute, Loyola University Medical Center, Maywood, IL 60153.
Abstract:
Burn injury results in alterations in granulocyte and macrophage production. Since macrophages may mediate these alterations we determined the effects of macrophages obtained from animals with burn injury with and without infection on the growth of marrow granulocyte macrophage progenitor cells (GM-CFCs). The in vitro GM-CFC growth response for maximally stimulated cultures was reduced by 25% to 30% (p < 0.01) for burned and infected (B + I) animal macrophages compared with burned (B) or sham (S) animals. Macrophages stimulated with endotoxin caused a further reduction for all groups in GM-CFC growth, most notably so for B + I macrophages. Burned + infected animal macrophages or all-endotoxin macrophages cocultured with indomethacin did not suppress GM-CFC growth. Following burn injury and infection, macrophages spontaneously elaborate negative regulators of myeloid growth that is further increased by endotoxin. It is likely that PGE2, a known negative regulator of granulocyte macrophage growth, is largely responsible for this suppressive effect.
Insights
Macrophages from burned and infected animals suppress myeloid progenitor cell growth. This effect is amplified by endotoxin and likely mediated by prostaglandin E2 (PGE2).
Area of Science:
- Immunology
- Hematology
Background:
- Burn injury significantly impacts immune cell production, particularly granulocytes and macrophages.
- Macrophages are suspected mediators of these post-burn immune alterations.
Purpose of the Study:
- To investigate the effect of macrophages from burned animals, with and without infection, on myeloid progenitor cell growth.
- To identify the mechanisms underlying macrophage-mediated suppression of granulocyte-macrophage progenitor cells (GM-CFCs) post-burn.
Main Methods:
- Co-culturing macrophages from sham, burned (B), and burned + infected (B + I) animals with marrow GM-CFCs.
- Stimulating macrophages with endotoxin and assessing GM-CFC growth.
- Investigating the role of prostaglandin E2 (PGE2) by co-culturing with indomethacin.
Main Results:
- Macrophages from B + I animals reduced in vitro GM-CFC growth by 25-30% compared to sham or B animals.
- Endotoxin stimulation further suppressed GM-CFC growth, especially with B + I macrophages.
- Indomethacin treatment blocked the suppressive effect of B + I or endotoxin-stimulated macrophages, suggesting a role for PGE2.
Conclusions:
- Macrophages from burned and infected animals spontaneously produce negative regulators of myeloid growth.
- Endotoxin exacerbates this suppression, with PGE2 being the likely key mediator.
- These findings highlight a mechanism for impaired myeloid recovery after severe burn injury and infection.