Spitzer J A, Zhang P, Mayer A M
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
J Leukoc Biol. 1994 Aug;56(2):166-73. doi: 10.1002/jlb.56.2.166.
Neutrophil accumulation in tissue is a hallmark of inflammation and is associated with a variety of pathological conditions. In bacterial infection neutrophils are selectively attracted in large numbers to phagocytose and kill invading microorganisms. However, activated neutrophils can also cause injury to tissues. To investigate functional alterations in liver recruited neutrophils (PMNs), we studied the functional characteristics of circulating blood and liver sequestered PMNs in terms of host defense mechanisms, such as nitric oxide (NO) and superoxide (SO) generation, beta 2 integrin expression, phagocytosis, and eicosanoid profile. Cells were isolated from rats infused with a nonlethal dose (320 micrograms/kg) of E. coli endotoxin (ET) or pyrogen-free saline for 90 min. Liver PMNs produced significantly more NO both in the absence and in the presence of an in vitro endotoxin challenge than did blood PMNs. No significant difference was observed in phorbol myristate acetate-stimulated SO generation. Endotoxin infusion significantly up-regulated the expression of CD11b/c in circulating and even more so in liver PMNs. Phagocytosis was significantly enhanced by in vivo ET treatment in blood PMNs, and liver PMNs showed even greater phagocytic activity than blood PMNs or Kupffer cells. The percent distribution of prostaglandins D2 and E2 of total 14C-eicosanoids was significantly higher and that of thromboxane B2 and 5-, 12-, and 15-HETEs was significantly lower in liver than in blood PMNs. Our study demonstrates several functional differences between liver-recruited and circulating PMNs in an acute endotoxic model. The implications of altered neutrophil function may extend to mechanisms of host defense and hepatotoxicity associated with sepsis and endotoxemia.
中性粒细胞在组织中的积聚是炎症的一个标志，并且与多种病理状况相关。在细菌感染中，中性粒细胞会被大量选择性地吸引，以吞噬和杀死入侵的微生物。然而，活化的中性粒细胞也会对组织造成损伤。为了研究肝脏募集的中性粒细胞（PMN）的功能改变，我们从宿主防御机制方面研究了循环血液和肝脏隔离的PMN的功能特性，如一氧化氮（NO）和超氧化物（SO）的产生、β2整合素的表达、吞噬作用以及类花生酸谱。细胞从用非致死剂量（320微克/千克）的大肠杆菌内毒素（ET）或无热原盐水灌注90分钟的大鼠中分离出来。与血液PMN相比，无论是在体外内毒素刺激不存在还是存在的情况下，肝脏PMN产生的NO都显著更多。在佛波酯肉豆蔻酸酯乙酸酯刺激的SO产生方面未观察到显著差异。内毒素灌注显著上调了循环中以及肝脏PMN中甚至更高水平的CD11b/c的表达。体内ET处理显著增强了血液PMN的吞噬作用，并且肝脏PMN显示出比血液PMN或库普弗细胞更大的吞噬活性。与血液PMN相比，肝脏中前列腺素D2和E2在总14C - 类花生酸中的百分比分布显著更高，而血栓素B2以及5 -、12 - 和15 - 羟基二十碳四烯酸（HETEs）的百分比分布显著更低。我们的研究证明了在急性内毒素模型中肝脏募集的PMN和循环PMN之间的几种功能差异。中性粒细胞功能改变的影响可能扩展到与脓毒症和内毒素血症相关的宿主防御机制和肝毒性。
