Holman J M, Saba T M
Department of Physiology, Albany Medical College, Union University, New York 12208.
J Leukoc Biol. 1988 Mar;43(3):193-203. doi: 10.1002/jlb.43.3.193.
We evaluated the concept that the vascular entrance of both bacterial and nonbacterial particulate material could lead to hepatic parenchymal cell injury, either due to postphagocytic Kupffer cell activity or the margination of activated leukocytes in the liver. Injection of denatured, collagen-coated particles as well as heat-killed bacteria were used as particulate challenges. Hepatic parenchymal cell injury in vivo during postoperative sepsis was evaluated by plasma aspartate aminotransferase (AST) and ornithine carbamyl transferase (OCT) enzyme levels over 3-72 h. AST and OCT levels elevated following either laparotomy plus cecal ligation (mild sepsis) or laparotomy plus cecal ligation with puncture (severe sepsis), with the peak level at 24 h. In addition, the direct intravenous injection of either nonbacterial foreign particles or heat-killed Pseudomonas aeruginosa into normal rats also produced a dose-dependent elevation of AST and OCT. The plasma level of either AST or OCT actually increased 350-400% after injection of the non-bacterial particles. A similar dose related elevation in enzymes followed the intravenous injection of heat-killed Pseudomonas. To differentiate the potential contribution of activated hepatic Kupffer cells versus activated marginated neutrophils to the in vivo hepatic injury, we determined the release of the hepatic specific enzyme OCT by cultured hepatic parenchymal cells when they were exposed to isolated Kupffer cells or isolated PMNs that were activated by exposure to dead bacteria. Bacteria alone when added to cultured hepatocytes did not induce significant OCT release. In contrast, activated PMNs but not Kupffer cells induced a significant (p less than 0.05) release of OCT from parenchymal cells into the culture media. Thus, in vivo transient hepatic parenchymal cell injury with post-operative sepsis may be mediated by the margination of activated PMNs in the liver.
我们评估了这样一种概念，即细菌和非细菌颗粒物质的血管进入可能导致肝实质细胞损伤，这要么是由于吞噬后库普弗细胞的活性，要么是由于肝脏中活化白细胞的边缘化。注射变性的、胶原包被的颗粒以及热灭活的细菌作为颗粒挑战物。通过术后3至72小时血浆中天冬氨酸转氨酶（AST）和鸟氨酸氨甲酰转移酶（OCT）的酶水平来评估术后脓毒症期间体内肝实质细胞损伤情况。在剖腹术加盲肠结扎（轻度脓毒症）或剖腹术加盲肠结扎并穿刺（重度脓毒症）后，AST和OCT水平升高，在24小时达到峰值。此外，向正常大鼠直接静脉注射非细菌异物颗粒或热灭活的铜绿假单胞菌也会导致AST和OCT呈剂量依赖性升高。注射非细菌颗粒后，AST或OCT的血浆水平实际上增加了350 - 400%。静脉注射热灭活的铜绿假单胞菌后，酶也出现了类似的剂量相关升高。为了区分活化的肝库普弗细胞与活化的边缘化中性粒细胞对体内肝损伤的潜在作用，我们测定了培养的肝实质细胞在暴露于经死菌激活的分离库普弗细胞或分离的多形核白细胞（PMN）时肝特异性酶OCT的释放情况。单独将细菌添加到培养的肝细胞中不会诱导显著的OCT释放。相反，活化的PMN而非库普弗细胞会导致实质细胞向培养基中显著（p小于0.05）释放OCT。因此，术后脓毒症时体内短暂的肝实质细胞损伤可能是由肝脏中活化的PMN的边缘化介导的。
