December 1994

Activation of Kupffer Cells In Vivo Following Femur Fracture

Author Affiliations

From the Departments of Surgery (Drs Huynh and Baker) and Cell Biology and Anatomy (Messrs Currin and Tanaka and Dr Lemasters), University of North Carolina School of Medicine, Chapel Hill.

Arch Surg. 1994;129(12):1324-1329. doi:10.1001/archsurg.1994.01420360114016

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.(Arch Surg. 1994;129:1324-1329)