Thermal injury induces the development of inflammatory macrophages from nonadherent bone marrow cells.
The normal course of hematopoiesis is controlled by growth factors and cytokines and, therefore, should be susceptible to alterations induced by systemic mediator release such as that seen following thermal injury. We hypothesized that a brief exposure of developing macrophages to the postthermal injury state would result in functionally altered progeny. We measured the production of inflammatory mediators by rat, bone-marrow macrophage precursors harvested 24 h following a 30% TBSA burn after subsequent maturation in a controlled, in vitro environment. Interleukin (IL)-6, tumor necrosis factor (TNF), and prostaglandin (PG) E2 levels in response to 24 h stimulation with lipopolysaccharide (LPS) were measured following 4 or 8 days of incubation with IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or both. Flow cytometric analysis showed that bone marrow cells harvested from burn and sham animals cultured in GM-CSF developed principally into macrophages (His48+, R21A6A+, CD11b+. Unstimulated cells produced negligent levels of cytokines and PGE2. Stimulated burn-derived cells released greater amounts of IL-6 and TNF at 4 or 8 days of culture depending on the conditions. Elevated PGE2 release was noted in all GM-CSF containing cultures, with burn-derived cells showing a trend towards reduced prostaglandin release. Detection of mRNA for cytokines after LPS stimulation showed no change in IL-6 or TNF transcripts. A short exposure to the systemic effects of thermal injury preprogramed macrophage progenitor cells with the propensity to develop into inflammatory macrophages, secreting higher levels of TNF and IL-6. This shift towards proinflammatory functions in these cells suggests they could be a source of enhanced inflammatory mediator release at 4 or more days post thermal injury.
Ogle
C K
CK
Department of Surgery, University of Cincinnati, Ohio, USA.
Valente
J F
JF
Guo
X
X
Li
B G
BG
Ogle
J D
JD
Alexander
J W
JW
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology* / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D018882:Heat Stress Disorders; D007249:Inflammation; D008264:Macrophages / Q000473:pathology* / Q000502:physiology; D051381:Rats