Activation of Kupffer cells in vivo following femur fracture
T. Huynh, R. T. Currin, Y. Tanaka, J. J. Lemasters and C. C. Baker
Department of Surgery, University of North Carolina School of Medicine, Chapel Hill.
OBJECTIVE: To test the hypothesis that Kupffer cells are activated after
blunt femur fracture leading to altered hepatic oxygen (O2) consumption.
DESIGN: Prospective randomized experimental trials. SETTING: Laboratory.
MATERIALS AND METHODS: Male Sprague-Dawley rats underwent closed femur
fracture with associated soft-tissue injury. Control animals received only
anesthesia. After 30 minutes and 2 hours, livers were perfused and fixed.
Tissue was processed for scanning and transmission electron microscopy. In
separate experiments, hepatic O2 consumption was measured in isolated
perfused livers 2 and 48 hours after femur fracture using a Clark-type
electrode. Oxygen consumption was calculated from the influent-effluent
concentration difference, flow rate, and liver weight. RESULTS: In
femur-fractured animals, scanning electron microscopy revealed alterations
in Kupffer cell surface characteristics, including increases in cell volume
and complex foldings and extensions of the plasma membrane. Transmission
electron microscopy showed internal vacuolization and dark-staining granule
formation. The changes were more pronounced 2 hours after femur fracture.
Hepatic O2 consumption increased significantly at both 2 and 48 hours after
femur fracture. Morphologic and functional activation of Kupffer cells were
not seen in control animals. CONCLUSION: In vivo ultrastructural evidence
shows Kupffer cell activation after closed femur fracture. This activation
is associated with increased hepatic O2 consumption, which is present at 2
hours and persists 48 hours following injury. The results suggest that
Kupffer cell activation may be related to the acute-phase response
following trauma.
