The effect of pegylated granulocyte colony-stimulating factor treatment prior to experimental mastitis in lactating Holsteins.
The effect of pegylated granulocyte colony-stimulating factor treatment prior to experimental mastitis in lactating Holsteins.
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哺乳期荷斯坦牛实验性乳腺炎前聚乙二醇化粒细胞集落刺激因子治疗的效果。
DOI：
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发表时间：
2018
影响因子：
3.5
通讯作者：
J. Lippolis
中科院分区：
文献类型：
--
作者：
E. J. Powell;T. Reinhardt;E. Casas;J. Lippolis
中性粒细胞是第一个行动和最突出的细胞防御乳腺炎引起的病原体。这使得中性粒细胞活化和扩增成为靶向治疗的明显候选者。粒细胞集落刺激因子（G-CSF）细胞因子刺激骨髓产生粒细胞和干细胞，并将其释放到血液中，这导致嗜中性粒细胞增多症以及增加血液中其他祖细胞的存在。聚乙二醇化形式的G-CSF（PEG-gCSF）已显示出显著降低产后奶牛中自然发生的乳腺炎率。尚未评价PEG-gCSF在实验性乳腺炎攻毒中的应用。为了研究PEG-gCSF治疗的效果和机制，我们通过乳房内输注11只泌乳中期的荷斯坦牛，用1000 cfu的大肠杆菌P4进行挑战。5头奶牛接受了2次PEG-gCSF注射，一次在疾病攻击前14 d，另一次在疾病攻击前7 d，6头奶牛未接受治疗。为了评价奶牛对PEG-gCSF治疗的反应，我们测量了全血细胞计数、体细胞计数、细菌计数、产奶量和摄食量数据。PEG-gCSF给药奶牛在每次PEG-gCSF注射后以及乳腺炎攻毒后，中性粒细胞和淋巴细胞的循环水平显著升高。PEG-gCSF治疗的奶牛在感染高峰期具有显著较低的细菌计数和较低的牛奶BSA水平。此外，与PEG-gCSF处理的奶牛相比，对照奶牛感染后产奶量显著降低，感染后采食量显著降低。总的来说，当在细菌攻击之前施用时，PEG-gCSF治疗导致疾病严重程度降低。从机制上讲，我们表明，G-CSF治疗增加了E-选择素配体的细胞表面表达之前，在血液中发现的中性粒细胞和单核细胞感染。这些细胞在感染后不久迅速从血液中消失，表明通过引发免疫细胞快速靶向感染部位来降低乳腺炎严重程度的机制。
Neutrophils are the first-acting and most prominent cellular defense against mastitis-causing pathogens. This makes neutrophil activation and expansion obvious candidates for targeted therapeutics. The granulocyte colony-stimulating factor (G-CSF) cytokine stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream, which results in neutrophilia as well as increasing the presence of other progenitor cells in the bloodstream. A pegylated form of G-CSF (PEG-gCSF) has been shown to significantly decrease naturally occurring mastitis rates in cows postpartum. The use of PEG-gCSF had not been evaluated in response to an experimental mastitis challenge. In an effort to examine the effect and mechanism of PEG-gCSF treatment, we challenged 11 mid-lactation Holsteins with ∼400 cfu Escherichia coli P4 by intramammary infusion. Five cows received 2 PEG-gCSF injections, one at 14 d and the other at 7 d before disease challenge, and 6 cows remained untreated. To evaluate the response of cows to the PEG-gCSF treatment, we measured complete blood counts, somatic cell counts, bacterial counts, milk yield, and feed intake data. The PEG-gCSF-treated cows had significantly increased circulating levels of neutrophils and lymphocytes after each PEG-gCSF injection, as well as following mastitis challenge. The PEG-gCSF-treated cows had significantly lower bacterial counts and lower milk BSA levels at the peak of infection. In addition, control cows had significant decreases in milk yield postinfection and significantly reduced feed intake postinfection compared with PEG-gCSF-treated cows. Collectively, PEG-gCSF treatment resulted in reduced disease severity when administered before a bacterial challenge. Mechanistically, we show that G-CSF treatment increases cell surface expression of an E-selectin ligand before infection on neutrophils and monocytes found in the blood. These cells quickly disappear from the blood shortly after infection, suggesting a mechanism for the reduced mastitis severity by priming immune cells for quick targeting to the site of infection.
DOI：
10.1016/j.tvjl.2007.12.031
发表时间：
2008-04
期刊：
Veterinary journal (London, England : 1997)
影响因子：
--
作者：
Sheldon IM;Williams EJ;Miller AN;Nash DM;Herath S
通讯作者：
Herath S