In vivo latex phagocytosis primes the Kupffer cells and hepatic neutrophils to generate superoxide anion. j Leukoc

Abstract: Activation of liver macrophages during clear-ance of endotoxins, bacteria, or other particulate materials may be accompanied by the migration of poly-morphonuclear neutrophils (PMNs) into the liver and priming of the hepatic phagocytes to release toxic oxygen metabolites. In the present study we investigated the effect of in vivo administration of latex particles on the hepatic sequestration of PMNs and the release of superox-ide anion (Of) by the in situ perfused rat liver and iso-lated hepatic phagocytes. One hour after an intravenous injection of latex beads, a significant amount of Of (0.7 nmol/min/g) was produced by the in situ perfused liver. Administration of latex particles into the perfused liver also elicited Of production. Hepatic phagocytes from latex-treated rats generated large amounts of 02 (2-14 nmol/60 min/106 cells) when these cells were stimulated in vitro with opsonized zymosan or phorbol myristate acetate (PMA), whereas phagocytes from saline-treated rats released less than 0.8 nmol 02. Intravenous infusion of superoxide dismutase or ibuprofen did not prevent the immigration of PMNs to the liver. However, ibuprofen inhibited the production of 02 by the perfused liver. Also, after addition of ibuprofen in vitro to isolated cells, there was more than 50 % inhibition of 02 generation by Kupffer cells and hepatic PMNs treated with either zymosan or PMA. These observations suggest that arachi-donic acid metabolites play a role in 02 release under these conditions. Thus, activation of the reticuloen-dothelial system by latex phagocytosis induces the migra-tion of PMNs into the liver and enhances the production of toxic oxygen-derived radicals by these cells and the resident Kupffer cells. The toxic oxygen radicals may also contribute to hepatic injury. J. Leukoc. Biol. 51