In vivo microscopic observations of the responses of Kupffer cells and the hepatic microcirculation to Mycobacterium bovis BCG alone and in combination with endotoxin.
Kupffer cell function and hepatic microvascular hemodynamics were studied by in vivo microscopy in Mycobacterium bovis BCG-infected NMRI mice before and after treatment with minute (0.01 mu mg) tolerance-producing doses and doses causing 70% lethality (0.5 micrograms) of Escherichia coli 0111:B5 endotoxin alone and in combination. BCG-induced granulomas distorted the hepatic microvasculature and impeded blood flow in many sinusoids; flow also was altered further by leukocytes adhering to the sinusoidal walls and by enlarged Kupffer cells that bulged into the lumen. Nevertheless, in BCG-infected mice, the ratio of Kupffer cells which phagocytosed latex to sinusoids containing blood flow and capable of delivering these particulates to Kupffer cells was significantly greater than that in uninfected mice. The phagocytosis of single latex particles by individual Kupffer cells also was more rapid. This indicated an expansion of the numbers and activation of Kupffer cells. In this hyperreactive state, the tolerance-inducing dose of endotoxin produced no change in the rate of phagocytosis after 2 h. In contrast, the 70% lethal dose reduced the rate by 123%, unless tolerance was induced, in which case there was no reduction in the rate of phagocytosis. Twenty-four hours after injection of the tolerance-inducing dose, however, the rate of phagocytosis was accelerated slightly (17%). This suggested that the Kupffer cells had been activated and perhaps were more effective in clearing subsequent endotoxin from the blood but without sufficient release of toxic substances to be lethal. That some mediators were released, however, was suggested by the microvascular alterations that accompanied the above phagocytic responses. These results further support the concept of a central role for Kupffer cells in endotoxin-mediated, nonspecific host defense mechanisms.
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006099:Granuloma / Q000473:pathology; D007700:Kinetics; D007728:Kupffer Cells / Q000276:immunology*; D008102:Liver Circulation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008833:Microcirculation; D009164:Mycobacterium Infections / Q000276:immunology* / Q000473:pathology; D009163:Mycobacterium bovis; D010587:Phagocytosis
D004731:Endotoxins