Cuzzocrea Salvatore, Rossi Antonietta, Serraino Ivana, Mazzon Emanuela, Di Paola Rosanna, Dugo Laura, Genovese Tiziana, Calabrò Barbara, Caputi Achille P, Sautebin Lidia
Department of Clinical and Experimental Medicine, University Federico II, Napoli, Italy.
J Leukoc Biol. 2003 Jun;73(6):739-46. doi: 10.1189/jlb.1002477.
In the present study, by comparing the responses in wild-type (WT) mice and mice lacking [knockout (KO)] the 5-lipoxygenase (5-LO), we investigated the role played by 5-LO in the development of acute inflammation. When compared with carragenan-treated 5-LOWT mice, 5-LOKO mice, which had received carrageenan, exhibited a reduced degree of pleural exudation, polymorphonuclear cell migration. Lung myeloperoxidase activity, an index of neutrophil infiltration, was significantly reduced in 5-LOKO mice in comparison with 5-LOWT. Lung-tissue sections from carrageenan-treated 5-LOWT mice showed positive staining for intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and E-selectin, which were mainly localized around vessels. The intensity and degree of ICAM-1, VCAM-1, P-selectin, and E-selectin were markedly reduced in tissue section from carrageenan-5-LOKO mice, which also improved the histological status of the inflamed lungs. Taken together, our results clearly demonstrate that 5-LO modulates neutrophil infiltration in the acute lung inflammation.
在本研究中,通过比较野生型(WT)小鼠和缺乏[基因敲除(KO)]5-脂氧合酶(5-LO)的小鼠的反应,我们研究了5-LO在急性炎症发展中所起的作用。与角叉菜胶处理的5-LOWT小鼠相比,接受角叉菜胶处理的5-LOKO小鼠的胸膜渗出、多形核细胞迁移程度降低。与5-LOWT小鼠相比,5-LOKO小鼠的肺髓过氧化物酶活性(中性粒细胞浸润的指标)显著降低。角叉菜胶处理的5-LOWT小鼠的肺组织切片显示细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)、P-选择素和E-选择素呈阳性染色,这些主要定位于血管周围。角叉菜胶-5-LOKO小鼠的组织切片中ICAM-1、VCAM-1、P-选择素和E-选择素的强度和程度显著降低,这也改善了炎症肺的组织学状态。综上所述,我们的结果清楚地表明,5-LO在急性肺炎症中调节中性粒细胞浸润。