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.