Triggiani M, Oriente A, Seeds M C, Bass D A, Marone G, Chilton F H
Division of Clinical Immunology and Allergy, University of Naples Federico II, School of Medicine, Italy.
J Exp Med. 1995 Nov 1;182(5):1181-90. doi: 10.1084/jem.182.5.1181.
Increasing evidence suggests that the metabolism of arachidonic acid (AA) may be different in inflammatory cells isolated from blood or migrating into tissues. To explore the possibility that changes in AA metabolism between blood and tissue inflammatory cells could be due in part to a different content or distribution of AA in glycerolipid classes, we studied these parameters in six human inflammatory cells isolated from blood (eosinophils, monocytes, neutrophils, and platelets) or from the lung tissue (mast cells and macrophages). Lung cells generally had a higher total cellular content of AA than that found in the blood cells. In addition, both mast cells and macrophages had a large endogenous pool of AA associated with triglycerides (TG), containing 45 and 22% of their total cellular AA, respectively. To address the hypothesis that cells migrating into the lung had a higher cellular level of AA and a larger AA pool in TG, we studied neutrophils isolated from the bronchoalveolar lavage (BAL) of patients with adult respiratory distress syndrome. BAL neutrophils had a fourfold increase in cellular AA as compared with blood neutrophils and contained 25% of their AA in TG versus 3% in blood neutrophils. BAL neutrophils also had a higher number of cytoplasmic lipid bodies (8 +/- 3/cell) relative to blood neutrophils (2 +/- 1/cell). High concentrations of free AA were also found in the cell-free BAL fluid of adult respiratory distress syndrome patients. To explore whether changes in BAL neutrophils may be due to the exposure of the cells to high concentrations of exogenous AA found in BAL, we incubated blood neutrophils in culture with AA (10-100 microM) for 24 h. Neutrophils supplemented with AA had a 10-fold increase in the amount of AA associated with TG and a sixfold increase in the number of lipid bodies. In addition, supplementation with AA induced a dose-dependent formation of hypodense cells. Taken together, these data indicate that human inflammatory cells undergo a fundamental and consistent remodeling of AA pools as they mature or enter the lung from the blood. These biochemical and morphological changes can be mimicked in vitro by exposing the cells to high levels of AA. This mechanism may be responsible for the changes in AA mobilization and eicosanoid metabolism observed in tissue inflammatory cells.
越来越多的证据表明，从血液中分离出的或迁移到组织中的炎性细胞中，花生四烯酸（AA）的代谢可能有所不同。为了探究血液和组织炎性细胞之间AA代谢变化可能部分归因于甘油脂质类别中AA含量或分布不同的可能性，我们研究了从血液中分离出的六种人类炎性细胞（嗜酸性粒细胞、单核细胞、中性粒细胞和血小板）或从肺组织中分离出的细胞（肥大细胞和巨噬细胞）的这些参数。肺细胞中AA的总细胞含量通常高于血细胞中的含量。此外，肥大细胞和巨噬细胞都有大量与甘油三酯（TG）相关的内源性AA池，分别占其总细胞AA的45%和22%。为了验证迁移到肺中的细胞具有更高的细胞内AA水平和更大的TG中AA池这一假设，我们研究了从成人呼吸窘迫综合征患者支气管肺泡灌洗（BAL）中分离出的中性粒细胞。与血液中的中性粒细胞相比，BAL中性粒细胞的细胞内AA增加了四倍，其AA的25%存在于TG中，而血液中性粒细胞中这一比例为3%。与血液中性粒细胞（2±1个/细胞）相比，BAL中性粒细胞的细胞质脂质体数量也更多（8±3个/细胞）。在成人呼吸窘迫综合征患者的无细胞BAL液中也发现了高浓度的游离AA。为了探究BAL中性粒细胞的变化是否可能是由于细胞暴露于BAL中发现的高浓度外源性AA所致，我们将血液中性粒细胞与AA（10 - 100微摩尔）在培养中孵育24小时。补充AA的中性粒细胞与TG相关的AA量增加了10倍，脂质体数量增加了6倍。此外，补充AA诱导了低密度细胞的剂量依赖性形成。综上所述，这些数据表明，人类炎性细胞在成熟或从血液进入肺的过程中经历了AA池的基本且一致的重塑。通过使细胞暴露于高水平的AA，这些生化和形态学变化在体外可以被模拟。这种机制可能是组织炎性细胞中观察到的AA动员和类花生酸代谢变化的原因。
