Burn wound infection-induced myeloid suppression: the role of prostaglandin E2, elevated adenylate cyclase, and cyclic adenosine monophosphate.
Suppressed granulocyte and macrophage growth after burn infection or endotoxicosis appears to be mediated by macrophage-derived products. In this study, we found that after burn, burn plus infection, or endotoxicosis, peritoneal-elicited macrophages or bone marrow cells released increased amounts of prostaglandin E2 (PGE2) and inhibited growth of granulocyte-macrophage progenitor cells (GM-CFC). PGE2, when added in culture, inhibited in vitro GM-CFC growth in a dose-dependent manner. Pretreatment of bone marrow cells with either dibutyryl cyclic adenosine monophosphate or Forskolin in vitro mimicked the PGE2 inhibition, further aggravated the inhibition induced by burn, burn plus infection, or endotoxicosis, and was not blocked by co-culture with indomethacin. Pretreatment of bone marrow cells with SQ22536, an adenylate cyclase inhibitor, significantly restored the suppressed GM-CFC growth found after burn, burn plus infection, or endotoxicosis. Alterations in myeloid production after burn infection appear to be related in part to the level of intracellular cyclic adenosine monophosphate for the GM-CFC and are responsive to PGE2.
Gamelli
R L
RL
Loyola University Medical Center, Shock Trauma Institute and Department of Surgery, Maywood, Illinois 60153, USA.
He
L K
LK
Liu
H
H
Ricken
J D
JD
D000262:Adenylyl Cyclases / Q000276:immunology*; D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D002056:Burns / Q000150:complications*; D000242:Cyclic AMP / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology*; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000209:etiology / Q000276:immunology*; D006098:Granulocytes / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D014946:Wound Infection / Q000209:etiology / Q000276:immunology*
D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone