Splenectomy alters Kupffer cell response to endotoxin
T. R. Billiar, M. A. West, B. J. Hyland and R. L. Simmons
Veterans of Foreign Wars Cancer Research Center, University of Minnesota Health Sciences Center, Minneapolis.
The spleen is a potential source for lymphokines, substances known to prime
or activate macrophages. Liver macrophages or Kupffer cells are directly
exposed to these products via the portal circulation. To determine whether
a loss of splenic factors would alter Kupffer cell responses, we studied
the effect of splenectomy or sham operation on Kupffer cell responses to
endotoxin lipopolysaccharide (LPS). We determined Kupffer cell activation
using an in vitro rat hepatocyte-Kupffer cell coculture system in which
Kupffer cells normally mediate a significant decrease in hepatocyte protein
synthesis if triggered by LPS. We found that Kupffer cells from
splenectomized rats were significantly less responsive to LPS three to 60
days after splenectomy. Kupffer cells from sham-operated animals responded
normally to LPS. This was contrasted to an increased sensitivity to LPS in
the first two days following splenectomy. These data suggest that both
splenectomy and a loss of splenic factors alter Kupffer cell responses to
septic stimuli. We propose that the decreased sensitivity to LPS after
splenectomy may be due to a loss of the priming effects of splenic
lymphokines. This decreased responsiveness might contribute to the
increased incidence of overwhelming infection after splenectomy.