Murine Kupffer cells. Mononuclear phagocytes deficient in the generation of reactive oxygen intermediates

Abstract

Murine Kupffer cells (KC) were isolated by a high yield collagenase perfusion technique. The morphology, surface markers, and secretory products were typical of macrophages in other tissues. However, KC released negligible levels of H2O2 and O-2, in contrast to peritoneal macrophages. KC oxygen consumption was not increased by agents triggering a respiratory burst in peritoneal cells. Moreover, KC capacity to secrete reactive oxygen intermediates (ROI), in contrast to Ia antigen expression, was not enhanced by exposure to lymphokines or recombinant gamma interferon. The selective defect in KC oxidative response was paralleled by impaired in vitro killing of Toxoplasma gondii trophozoites and Leishmania donovani promastigotes and amastigotes. Deficient secretion of ROI by KC might protect hepatocytes and erythrocytes from injury during endocytosis by KC, but might render the liver more susceptible to parasitization by organisms that are primarily killed through oxygen-dependent mechanisms.