Investigations on the Etiology of Sepsis by Using Experimental Mouse Model with Leukocytopenia

: In the previous report, we showed that the reticuloendothelial system (RES), especially the liver, played an important role in the etiology of bacteremia or sepsis as the major protective system. In this study, to investigate the role of Kupffer cells in the etiology of bacteremia, we isolated and cultured murine Kupffer cells using a technique involving perfusion with collagenase and DNase. We compared the adherence and phagocytosis rate of two groups of isolated bacteria from bacteremic mice by these cells. One group was bacteria causing systemic bacteremia consisted of P. aeruginosa and M. morganii, and the other was bacteria causing portal bacteremia consisted of E. coli, E. cloacae, K. pneumoniae and Enterococci. As a consequence, the following facts were revealed. 1. The bacterial phagocytosis and adherence rate by Kupffer cells were significantly higher in bacteria causing portal bacteremia than in bacteria causing systemic bacteremia. These data were correlated to each blood clearance rate from mice. 2. Blood clearance rate reflected mainly adherence of Kupffer cells to bacteria, and it was suggested that these adherence were one of the most important factor to protect the hosts from the advance of bacteremia from the portal to the systemic. 3. In the case of using peritoneal macrophage, we couldn't find the same correlation, so the possibility was suggested that the above phenomenon was specific to Kupffer cells.