Faculty of Veterinary Medicine, Department of Internal Medicine, Reproduction and Population Medicine, Ghent University, Merelbeke, Ghent, Belgium.
Department of Veterinary Sciences, University of Turin, Grugliasco, Turin, Italy.
PLoS One. 2024 Oct 10;19(10):e0311742. doi: 10.1371/journal.pone.0311742. eCollection 2024.
In dairy cattle research, in vitro assessment of innate immune function is commonly evaluated by flow cytometry via the quantitative analysis of circulating polymorphonuclear leukocytes (PMN) functionalities specifically focusing on the capacities for phagocytosis (PC) and oxidative burst (OB). Variations in these PMN functions, however, may not only be influenced by the health status of the animals but also by technical, non-animal related factors. Our objectives were to assess the PMN viability, PC and OB capacities from blood samples collected in tubes coated with different anticoagulants (acid citrate dextrose (ACD) and ethylenediaminetetraacetic acid (EDTA)) and stored for 0, 3, 6, 9, and 12 h at 4°C (to mimic transportation timeframe). Furthermore, we evaluated the PMN functionalities (PC and OB) in samples incubated in culture medium with glucose (7.2 mM) versus no glucose. Over five replicates, coccygeal blood samples were collected from three nulliparous Holstein heifers (5 ACD and 5 EDTA per heifer) and allocated in a refrigerated container (4°C) for 0, 3, 6, 9, and 12 h. At each time point, PMN were isolated using gradient centrifugation. Immunolabeled PMN (CH138A) were subjected to a tricolor fluorescent staining to evaluate their viability (viable, apoptotic, and necrotic PMN). Phagocytosis and OB were assessed by incubating PMN with fluorescent beads and by phorbol 12-myristate 13-acetate stimulation, respectively. The effects of anticoagulant type, storage time, and presence of glucose in the culture medium on PMN viability and function parameters were fitted in mixed linear regression models. The proportion of viable PMN at 0 h was similar for ACD and EDTA (92 ± 4.6% and 93 ± 4.6%, respectively) but it decreased to 78 ± 4.6% for ACD and 79 ± 4.6% for EDTA after 6 h of storage. The proportion of viable PMN was not different between ACD and EDTA at any time point. The proportion of PMN that engulfed beads (PC percentage) and the PC median fluorescence intensity (MFI) reached their highest value after 3 h of storage compared with the other time points. However, the anticoagulant type (ACD versus EDTA) and the presence of glucose in the culture medium did not influence these PC parameters. Oxidative burst MFI was higher in PMN incubated in glucose-supplemented culture medium versus no glucose. We demonstrated that technical factors interfere with the evaluation of PMN viability and functionality, which can potentially lead to bias in the findings of a research hypothesis. To conclude, the present study showed that the optimal timeframe for performing PMN function analyses is within 3 hours after blood sampling. Furthermore, the presence of 7.2 mM glucose in the culture medium, a common concentration in formulation of cell culture medium, increases the in vitro OB capacity, potentially masking any impairments in in vivo PMN dysfunctionality.
在奶牛研究中,通常通过流式细胞术对固有免疫功能进行体外评估,通过定量分析循环中性粒细胞(PMN)的功能来专门评估吞噬作用(PC)和氧化爆发(OB)的能力。然而,PMN 功能的变化不仅可能受到动物健康状况的影响,还可能受到与技术相关的非动物因素的影响。我们的目标是评估从涂有不同抗凝剂(柠檬酸葡萄糖(ACD)和乙二胺四乙酸(EDTA))的管中收集的血液样本中的PMN 活力、PC 和 OB 能力,并在 4°C 下储存 0、3、6、9 和 12 小时(模拟运输时间)。此外,我们评估了在含有葡萄糖(7.2mM)和不含葡萄糖的培养基中孵育的 PMN 功能(PC 和 OB)。在五个重复中,从三头初产荷斯坦奶牛(每头奶牛 5 个 ACD 和 5 个 EDTA)采集尾椎血样,并在冷藏容器(4°C)中放置 0、3、6、9 和 12 小时。在每个时间点,使用梯度离心法分离 PMN。用三色荧光染色标记 PMN(CH138A),以评估其活力(活、凋亡和坏死 PMN)。吞噬作用和 OB 通过用荧光珠孵育 PMN 和用佛波醇 12-肉豆蔻酸 13-乙酸刺激来评估。抗凝剂类型、储存时间和培养基中葡萄糖对 PMN 活力和功能参数的影响在混合线性回归模型中进行拟合。0 小时时 ACD 和 EDTA 的活 PMN 比例相似(分别为 92±4.6%和 93±4.6%),但储存 6 小时后,ACD 的活 PMN 比例降至 78±4.6%,EDTA 的活 PMN 比例降至 79±4.6%。在任何时间点,ACD 和 EDTA 之间的活 PMN 比例均无差异。与其他时间点相比,储存 3 小时后 PMN 吞噬珠的比例(PC 百分比)和 PC 中荧光强度(MFI)达到最高值。然而,抗凝剂类型(ACD 与 EDTA)和培养基中葡萄糖的存在并不影响这些 PC 参数。在含有葡萄糖的培养基中孵育的 PMN 的氧化爆发 MFI 高于不含葡萄糖的培养基。我们证明了技术因素会干扰 PMN 活力和功能的评估,这可能导致对研究假设的发现产生偏差。总之,本研究表明,进行 PMN 功能分析的最佳时间框架是在采血后 3 小时内。此外,培养基中存在 7.2mM 葡萄糖(细胞培养基配方中的常见浓度)增加了体外 OB 能力,可能掩盖了体内 PMN 功能障碍的任何损害。