AJP - Gastrointestinal and Liver Physiology, Vol 272, Issue 6 1457-G1462, Copyright © 1997 by American Physiological Society
Adaptive Kupffer cell alterations after femur fracture trauma in rats
T. Huynh, C. C. Baker, L. W. Bracey and J. J. Lemasters
Department of Surgery, University of North Carolina School of Medicine, Chapel Hill 27599-7210, USA.
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.
