ADAPTIVE KUPFFER CELL ALTERATIONS AFTER FEMUR FRACTURE TRAUMA IN RATS

Because Kupffer cells constitute the largest fixed macrophage populati on and reside at a strategic position in hepatic sinusoids, interactin g with hepatocytes, circulating cells, and mediators hom the gut, they may be important in the inflammatory response after injury. This stud y examined the effect of remote tissue injury on Kupffer cell function . Femurs of Sprague-Dawley rats were fractured under anesthesia. Subse quently, their Livers were perfused for measurement of oxygen consumpt ion and the isolation and culture of Kupffer cells. At 2 and 48 h afte r femur fracture, hepatic oxygen consumption increased 17 and 19%, res pectively. Gadolinium chloride pretreatment to ablate Kupffer cells bl acked 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 stimulate d by phorbol ester increased eightfold, phagocytosis increased fourfol d, and lipopolysaccharide (LPS)-stimulated prostaglandin E-2 increased sixfold in comparison to sham-operated controls. In contrast, LPS-sti mulated tumor necrosis factor-a and nitric oxide production decreased 50 and. 60%, respectively. These data show that peripheral trauma rapi dly induces changes in hepatic macrophages characterized by adaptation to a more antimicrobial and less proinflammatory phenotype.