Adaptive Kupffer cell alterations after femur fracture trauma in rats.
Because Kupffer cells constitute the largest fixed macrophage population and reside at a strategic position in hepatic sinusoids, interacting with hepatocytes, circulating cells, and mediators from the gut, they may be important in the inflammatory response after injury. This study examined the effect of remote tissue injury on Kupffer cell function. Femurs of Sprague-Dawley rats were fractured under anesthesia. Subsequently, their livers were perfused for measurement of oxygen consumption and the isolation and culture of Kupffer cells. At 2 and 48 h after femur fracture, hepatic oxygen consumption increased 17 and 19%, respectively. Gadolinium chloride pretreatment to ablate Kupffer cells blocked this increase of hepatic oxygen consumption after femur fracture but had no effect in sham-operated animals. In Kupffer cells isolated and cultured 2 h after femur fracture, superoxide formation stimulated by phorbol ester increased eightfold, phagocytosis increased fourfold, and lipopolysaccharide (LPS)-stimulated prostaglandin E2 increased sixfold in comparison to sham-operated controls. In contrast, LPS-stimulated tumor necrosis factor-alpha and nitric oxide production decreased 50 and 60%, respectively. These data show that peripheral trauma rapidly induces changes in hepatic macrophages characterized by adaptation to a more antimicrobial and less proinflammatory phenotype.
Huynh
T
T
Department of Surgery, University of North Carolina School of Medicine, Chapel Hill 27599-7210, USA.
Baker
C C
CC
Bracey
L W
LW
Lemasters
J J
JJ
D000818:Animals; D002478:Cells, Cultured; D004926:Escherichia coli; D005264:Femoral Fractures / Q000503:physiopathology*; D005682:Gadolinium / Q000494:pharmacology; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D010101:Oxygen Consumption / Q000187:drug effects; D010587:Phagocytosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide; D005682:Gadolinium; C038958:gadolinium chloride