Department of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, AL9 7TA, United Kingdom.
Elanco Animal Health, Eli Lilly and Company Ltd., Basingstoke, RG24 9NL, United Kingdom.
J Dairy Sci. 2019 Oct;102(10):9389-9395. doi: 10.3168/jds.2019-16563. Epub 2019 Jul 17.
In periparturient dairy cows, immune suppression, resulting in decreased neutrophil numbers and function, leads to increased susceptibility to postpartum conditions such as mastitis, retained placenta, and metritis. Administration of polyethylene glycol-conjugated bovine granulocyte colony stimulating factor (pegbovigrastim, Imrestor; Elanco Animal Health, Greenfield, IN) 7 d before and within 24 h of calving, effectively improves granulocyte production and function in vivo as well as in milk. A recently developed coculture assay was adapted for use with endometrial epithelial cells to assess the effects of pegbovigrastim application on directed granulocyte migration and bactericidal activity in vitro on a per-cell basis in endometrial cell cultures. Granulocytes from treated and untreated periparturient cows (6 and 5 per group, respectively) were evaluated for their ability to migrate to and kill bacteria after treatment, in context of the infected endometrium. We hypothesized that in addition to increasing the absolute concentration of circulating neutrophil granulocytes, pegbovigrastim treatment in vivo alters the ability of granulocytes to migrate to endometrial cells in vitro. The results clearly show a marked increase in the total concentration of granulocytes and monocytes between the 2 treatment groups as early as 2 d after the first injection, and this increased between the samples taken 2 d after calving. No migratory or killing differences were identified between granulocytes of both groups, suggesting that pegbovigrastim-induced granulocytes were as effective as non-induced cells. This may also be due to the absence of negative energy balance in the study animals and leads us to conclude that the positive effects seen in vivo are most likely based on the larger number of granulocytes present rather than a direct effect of pegbovigrastim treatment on the functionality of cells for the parameters tested in this study.
围产期奶牛的免疫抑制导致中性粒细胞数量和功能下降，从而增加了产后发生乳腺炎、胎衣不下和子宫炎等疾病的易感性。在分娩前 7 天和分娩后 24 小时内给予聚乙二醇结合牛粒细胞集落刺激因子（pegbovigrastim，Imrestor；Elanco Animal Health，Greenfield，IN），可有效改善体内和牛奶中粒细胞的生成和功能。最近开发的共培养测定法被改编用于子宫内膜上皮细胞，以评估 pegbo-vigrastim 应用对体外子宫内膜细胞培养中定向粒细胞迁移和杀菌活性的影响。分别从接受和未接受围产期奶牛（每组 6 头和 5 头）中评估处理后粒细胞向受感染子宫内膜迁移和杀菌的能力。我们假设，除了增加循环中性粒细胞的绝对浓度外，pegbo-vigrastim 治疗还会改变粒细胞在体内向子宫内膜细胞迁移的能力。结果清楚地表明，在第一次注射后 2 天，两组之间的粒细胞和单核细胞的总浓度明显增加，并且在分娩后 2 天的样本之间增加。两组粒细胞之间没有发现迁移或杀伤差异，这表明 pegbo-vigrastim 诱导的粒细胞与非诱导细胞一样有效。这也可能是由于研究动物中不存在负能平衡，因此我们得出结论，在体内观察到的积极影响很可能是基于存在更多的粒细胞，而不是 pegbo-vigrastim 处理对本研究中测试的参数的细胞功能的直接影响。
