Scott Melanie J, Cheadle William G, Hoth J Jason, Peyton James C, Subbarao Krishnaprasad, Shao Wen-Hai, Haribabu Bodduluri
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Clin Diagn Lab Immunol. 2004 Sep;11(5):936-41. doi: 10.1128/CDLI.11.5.936-941.2004.
Leukotriene B4 (LTB4) is a rapidly synthesized, early neutrophil chemoattractant that signals via its cell surface receptor, BLT-1, to attract and activate neutrophils during peritonitis. BLT-1-deficient (BLT-1(-/-)) mice were used to determine the effects of LTB4 on neutrophil migration and activation, bacterial levels, and survival after cecal ligation and puncture (CLP). Male BLT-1(-/-) or wild-type (WT) BALB/c mice underwent CLP. Tissues were harvested for determination of levels of bacteria, myeloperoxidase (MPO), LTB4, macrophage inflammatory protein 2 (MIP-2), and neutrophil (polymorphonuclear leukocyte [PMN]) numbers at 4 and 18 h after CLP. PMN activation was determined by an assessment of phagocytosis ability and CD11b expression. Survival was also determined. BLT-1(-/-) mice had decreased numbers of PMNs in the peritoneum at both 4 and 18 h after CLP but increased numbers of PMNs in the blood at 18 h compared with WT mice. Liver and lung MPO levels were significantly higher in BLT-1(-/-) mice at both 4 and 18 h after CLP, with increased bacterial levels in the blood, the liver, and peritoneal fluid at 4 h. Bacterial levels remained higher in peritoneal fluid at 18 h, but blood and liver bacterial levels at 18 h were not different from levels at 4 h. PMN phagocytosis and CD11b levels were decreased in BLT-1(-/-) mice. LTB4 levels were similar between the groups before and after CLP, but MIP-2 levels were decreased both locally and systemically in BLT-1(-/-) mice. Survival was significantly improved in BLT-1(-/-) mice (71%) compared with WT mice (14%) at 48 h post-CLP. Thus, LTB4 modulates neutrophil migration into the mouse peritoneum, but not the lung or liver, after CLP. Despite higher bacterial and PMN levels at remote sites, there was increased survival in BLT-1(-/-) mice compared to WT mice. Decreased PMN activation may result in less remote organ dysfunction and improved survival.
白三烯B4（LTB4）是一种快速合成的早期中性粒细胞趋化因子，它通过其细胞表面受体BLT-1发出信号，在腹膜炎期间吸引并激活中性粒细胞。利用BLT-1基因缺陷（BLT-1(-/-)）小鼠来确定LTB4对盲肠结扎穿孔（CLP）术后中性粒细胞迁移与激活、细菌水平及存活率的影响。雄性BLT-1(-/-)或野生型（WT）BALB/c小鼠接受CLP手术。在CLP术后4小时和18小时采集组织，用于测定细菌、髓过氧化物酶（MPO）、LTB4、巨噬细胞炎性蛋白2（MIP-2）水平以及中性粒细胞（多形核白细胞[PMN]）数量。通过评估吞噬能力和CD11b表达来确定PMN激活情况。同时也测定存活率。与WT小鼠相比，BLT-1(-/-)小鼠在CLP术后4小时和18小时腹膜内的PMN数量减少，但在18小时时血液中的PMN数量增加。CLP术后4小时和18小时，BLT-1(-/-)小鼠肝脏和肺组织中的MPO水平显著更高，4小时时血液、肝脏和腹腔液中的细菌水平升高。18小时时腹腔液中的细菌水平仍较高，但18小时时血液和肝脏中的细菌水平与4小时时无差异。BLT-1(-/-)小鼠的PMN吞噬作用和CD11b水平降低。CLP术前和术后两组间LTB4水平相似，但BLT-1(-/-)小鼠局部和全身的MIP-2水平均降低。CLP术后48小时，与WT小鼠（14%）相比，BLT-1(-/-)小鼠的存活率显著提高（71%）。因此，CLP术后LTB4调节中性粒细胞向小鼠腹膜内的迁移，但不调节向肺或肝脏的迁移。尽管远处部位的细菌和PMN水平较高，但与WT小鼠相比，BLT-1(-/-)小鼠的存活率有所提高。PMN激活减少可能导致远处器官功能障碍减轻及存活率提高。
