Alteration of Rat Kupffer Cell Function Following Mitomycin-C Administration

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Abstract
Cancer chemotherapeutic agents modify the human immune system in diverse ways including both immunosuppression and immunostimulation. We evaluated the effects of mitomycin-C on rat Kupffer cell phagocytosis, C3b receptor binding, and lysosomal enzyme activity. Kupffer cell cultures were greater than 95% pure. Phagocytosis of IgG-coated sheep red blood cells was demonstrated by 84% of control cells but by only 25% of cells isolated two weeks following mitomycin-C administration (p < 0.0005). This depression in phagocytic ability had returned to control levels by four weeks post-treatment. Similarly, C3b receptor binding of IgM and complement coated sheep red blood cells was observed in 88% of control Kupffer cells, but declined to 47% at two weeks after drug administration (p < 0.005) and returned to normal after four weeks. Lysosomal enzyme activity was not impaired by mitomycin-C. Histologically severe ulceratlon of the colon of treated animals was seen one and two weeks after drug administration, but healed by four weeks post-mitomycin-C treatment. Depression of macrophage function as a consequence of cancer chemotherapy may have important clinical consequences in host defense against bacteria and tumor metastases.