Proinflammatory kupffer cell alterations after femur fracture trauma and sepsis in rats.
This study examined effects of trauma and sepsis on Kupffer cell function. When CBA/J mice had femur fracture (FFx), no deaths occurred. After cecal ligation and puncture (CLP), 44% died. Following combined injuries (FFx + CLP), mortality increased to 60%, suggesting a deleterious effect between FFx + CLP. Kupffer cell ablation with GdCI3 decreased mortality to 13% after CLP and 5% after FFx + CLP. After FFx, CLP, and FFx + CLP, Kupffer cells isolated from Sprague-Dawley rats produced 720%, 1,100%, and 2,130% more O2. than sham, respectively. Phagocytosis increased 320%, 610%, and 150%. Kupffer cell PGE2 production also increased 300%, 510%, and 300% over sham. After FFx alone, TNF-alpha production decreased 40%. By contrast, CLP and FFx + CLP increased TNF-alpha release 25% and 100%, respectively. After FFx, NO. production decreased 44%, whereas NO increased 280% and 260% after CLP and FFx + CLP. These findings indicate that Kupffer cells mediate mortality after CLP and FFx + CLP. Increased mortality is associated with a more proinflammatory and less antimicrobial Kupffer cell phenotype.
Huynh
T
T
Carolinas Medical Center, The University of North Carolina School of Medicine, Chapel Hill 27599-7210, USA.
Lemasters
J J
JJ
Bracey
L W
LW
Baker
C C
CC
D000818:Animals; D002432:Cecum / Q000382:microbiology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity; D004926:Escherichia coli; D005264:Femoral Fractures / Q000150:complications / Q000503:physiopathology*; D007728:Kupffer Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008811:Mice, Inbred DBA; D009569:Nitric Oxide / Q000502:physiology; D010587:Phagocytosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000209:etiology / Q000503:physiopathology*; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D015232:Dinoprostone