The role of the Kupffer cell in the infection of rodents by sporozoites of Plasmodium: uptake of sporozoites by perfused liver and the establishment of infection in vivo.

The uptake of Plasmodium yoelii nigeriensis sporozoites by isolated perfused rat liver was very rapid and efficient. 67% of the initial load was removed from the perfusion media in the first passage through the liver, and 95% after 15 min of perfusion. Much of the uptake was explained by mechanical trapping in the liver. Up to 75% of the sporozoite load was retained after 15 min both by heat killed liver and liver cooled to 4 degrees C, therefore at least 20% of the sporozoite uptake in perfused normal livers was due to a biologically active process. In perfused normal livers, non-infective (heat-killed or trypsin-treated) sporozoites were taken up with an efficiency equal to infective sporozoite controls. However, a reduction in Kupffer cell number and activity, induced by silica treatment, resulted in a very significant decline in uptake of infective sporozoites by the perfused liver--and a parallel fall in the successful infection of the host by inoculated sporozoites in vivo. Since silica treatment produced no significant detectable pathological changes in hepatocytes, and infected blood passage results in a normal parasitaemia in silica treated animals it was concluded that the Kupffer cell was a component of the natural route of infection of the mammalian host by the majority of the infecting population of sporozoites of Plasmodium yoelii nigeriensis.