Filipovich Yana, Agrawal Varkha, Crawford Susan E, Fitchev Philip, Qu Xiaowu, Klein Jeremy, Hirsch Emmet
Department of Obstetrics and Gynecology, NorthShore University HealthSystem, Evanston, IL.
Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO.
Am J Obstet Gynecol. 2015 Nov;213(5):697.e1-10. doi: 10.1016/j.ajog.2015.07.025. Epub 2015 Jul 26.
The objective of the study was to investigate the role of polymorphonuclear leukocytes (PMNs) in a mouse model of Escherichia coli-induced labor.
Intraperitoneal injection of rabbit antimouse PMN antiserum or control was performed in CD-1 mice 29 hours and 5 hours prior to laparotomy and intrauterine injection of either killed E coli or phosphate-buffered saline on day 14.5 of pregnancy. Preterm delivery was defined as delivery of at least 1 pup within 48 hours. Circulating leukocyte counts were determined manually or by flow cytometry at the time of surgery and 8, 24, and 48 hours afterward. Maternal and fetal tissues were analyzed in a separate group of animals 8 hours after surgery.
Pretreatment with anti-PMN antiserum significantly decreased the numbers of circulating leukocytes and the proportion of neutrophils among all leukocytes by 70-80% at surgery and at least 8 hours thereafter. Neutrophil depletion significantly reduced 2 markers of neutrophil activation in the uterus and placenta (neutrophil elastase and myeloperoxidase activity) and neutrophil infiltration into gestational tissues in bacterially treated animals to baseline (control) levels but did not affect preterm birth rates. The large E coli-induced increases in uterine inflammatory markers (interleukin-1β, tumor necrosis factor, chemokine ligand-5, cyclooxygenase-2) were not affected or were only minimally affected by neutrophil depletion.
Although PMN antiserum reduces both neutrophil number and activity, it does not diminish sensitivity to bacterially induced delivery or meaningfully alter the expression of inflammatory markers in the mouse model. Preterm birth and inflammation in this model are not likely to depend on neutrophil function.
本研究的目的是在大肠杆菌诱导分娩的小鼠模型中研究多形核白细胞(PMN)的作用。
在妊娠第14.5天进行剖腹手术和子宫内注射灭活大肠杆菌或磷酸盐缓冲盐水前29小时和5小时,对CD-1小鼠进行腹腔注射兔抗小鼠PMN抗血清或对照。早产定义为在48小时内分娩至少1只幼崽。在手术时以及术后8、24和48小时手动或通过流式细胞术测定循环白细胞计数。在另一组动物术后8小时分析母体和胎儿组织。
抗PMN抗血清预处理在手术时及之后至少8小时显著降低循环白细胞数量以及所有白细胞中中性粒细胞的比例达70 - 80%。中性粒细胞耗竭显著降低细菌处理动物子宫和胎盘中中性粒细胞活化的2个标志物(中性粒细胞弹性蛋白酶和髓过氧化物酶活性)以及中性粒细胞向妊娠组织的浸润至基线(对照)水平,但不影响早产率。大肠杆菌诱导的子宫炎症标志物(白细胞介素-1β、肿瘤坏死因子、趋化因子配体-样5、环氧化酶-2)的大幅增加不受中性粒细胞耗竭影响或仅受到轻微影响。
尽管PMN抗血清可降低中性粒细胞数量和活性,但在小鼠模型中它不会降低对细菌诱导分娩的敏感性或有意义地改变炎症标志物的表达。该模型中的早产和炎症不太可能依赖于中性粒细胞功能。