In vivo latex phagocytosis primes the Kupffer cells and hepatic neutrophils to generate superoxide anion.
Activation of liver macrophages during clearance of endotoxins, bacteria, or other particulate materials may be accompanied by the migration of polymorphonuclear 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 superoxide anion (O2-) by the in situ perfused rat liver and isolated hepatic phagocytes. One hour after an intravenous injection of latex beads, a significant amount of O2- (0.7 nmol/min/g) was produced by the in situ perfused liver. Administration of latex particles into the perfused liver also elicited O2- production. Hepatic phagocytes from latex-treated rats generated large amounts of O2- (2-14 nmol/60 min/10(6) 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 O2-. Intravenous infusion of superoxide dismutase or ibuprofen did not prevent the immigration of PMNs to the liver. However, ibuprofen inhibited the production of O2- by the perfused liver. Also, after addition of ibuprofen in vitro to isolated cells, there was more than 50% inhibition of O2- generation by Kupffer cells and hepatic PMNs treated with either zymosan or PMA. These observations suggest that arachidonic acid metabolites play a role in O2- release under these conditions. Thus, activation of the reticuloendothelial system by latex phagocytosis induces the migration 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.
Bautista
A P
AP
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Schuler
A
A
Spolarics
Z
Z
Spitzer
J J
JJ
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002469:Cell Separation; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007728:Kupffer Cells / Q000378:metabolism* / Q000502:physiology; D007840:Latex / Q000008:administration & dosage; D008099:Liver / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D007840:Latex; D013481:Superoxides; D015054:Zymosan; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen; D007052:Ibuprofen