Prostaglandin E2 receptor antagonist (SC-19220) treatment restores the balance to bone marrow myelopoiesis after burn sepsis.
BACKGROUND
Although prostaglandin E2 (PGE2) has been shown to be immunosuppressive, its role in the development of specific bone marrow myeloid lineages after thermal injury and sepsis has yet to be elucidated. The purpose of this study was to demonstrate that alterations in bone marrow progenitor proliferation favoring monocytopoiesis in burn sepsis can be restored by blocking the cellular interactions of PGE2.


METHODS
A murine model of burn sepsis with and without treatment with SC-19220, a PGE2 receptor antagonist, was used to determine peripheral monocyte and neutrophil counts as well as the colony forming potential of colony-stimulating factor responsive bone marrow progenitors.


RESULTS
Burn sepsis augmented the growth of the early colony-forming unit granulocyte-macrophage and monocyte progenitors and the number of circulating monocytes, whereas granulocyte progenitors and circulating neutrophils demonstrated an opposite response. Treatment with SC-19220 nearly reversed these alterations.


CONCLUSIONS
These data indicate that abrogating PGE2's actions during burn sepsis can restore the balance in bone marrow granulocyte and monocyte production, further consolidating the pivotal role PGE2 plays in the pathogenesis of burn sepsis.
Santangelo
S
S
Loyola University Medical Center, Maywood, Illinois 60153, USA.
Shoup
M
M
Gamelli
R L
RL
Shankar
R
R
D000818:Animals; D002056:Burns / Q000150:complications*; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000276:immunology; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology; D007958:Leukocyte Count / Q000187:drug effects; D019891:Leukopoiesis / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D011552:Pseudomonas Infections / Q000097:blood / Q000188:drug therapy* / Q000209:etiology* / Q000276:immunology; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors* / Q000276:immunology; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology* / Q000276:immunology
D018078:Receptors, Prostaglandin E; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide