Bautista A P, Schuler A, Spolarics Z, Spitzer J J
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
J Leukoc Biol. 1992 Jan;51(1):39-45. doi: 10.1002/jlb.51.1.39.
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.
在内毒素、细菌或其他颗粒物质清除过程中，肝巨噬细胞的激活可能伴随着多形核中性粒细胞（PMN）向肝脏的迁移以及肝吞噬细胞的致敏，从而释放有毒的氧代谢产物。在本研究中，我们调查了体内给予乳胶颗粒对PMN在肝脏中的滞留以及原位灌注大鼠肝脏和分离的肝吞噬细胞释放超氧阴离子（O2-）的影响。静脉注射乳胶珠1小时后，原位灌注肝脏产生了大量的O2-（0.7 nmol/分钟/克）。向灌注肝脏中给予乳胶颗粒也引发了O2-的产生。当用调理酵母聚糖或佛波醇肉豆蔻酸酯乙酸酯（PMA）在体外刺激时，来自乳胶处理大鼠的肝吞噬细胞产生大量的O2-（2 - 14 nmol/60分钟/10(6)个细胞），而来自生理盐水处理大鼠的吞噬细胞释放的O2-少于0.8 nmol。静脉输注超氧化物歧化酶或布洛芬并不能阻止PMN向肝脏的迁移。然而，布洛芬抑制了灌注肝脏中O2-的产生。此外，在体外向分离的细胞中加入布洛芬后，用酵母聚糖或PMA处理的库普弗细胞和肝PMN产生的O2-受到超过50%的抑制。这些观察结果表明，花生四烯酸代谢产物在这些条件下的O2-释放中起作用。因此，通过乳胶吞噬作用激活网状内皮系统会诱导PMN向肝脏迁移，并增强这些细胞和常驻库普弗细胞产生有毒的氧衍生自由基。有毒的氧自由基也可能导致肝损伤。
