The objective of this study was to determine the effect of pulmonary intravascular macrophage depletion on systemic inflammation and ex vivo neutrophil apoptosis, using an experimental model of intestinal ischemia and reperfusion injury in horses. Neutrophils were isolated before and after surgery from horses that were randomized to 3 treatment groups: sham celiotomy (CEL, n=4), intestinal ischemia and reperfusion (IR, n=6), intestinal ischemia and reperfusion with gadolinium chloride treatment to deplete pulmonary intravascular macrophages (PIMs, IRGC, n=6). Neutrophil apoptosis was assessed with Annexin V and propidium iodide staining quantified with flow cytometry and caspase-3, -8, and -9 activities in neutrophil lysates. All horses experienced a systemic inflammatory response following surgery. Following surgery, ex vivo neutrophil apoptosis was significantly delayed after 12 or 24 h in culture, except in IRGC horses (12 h: CEL: P = 0.03, IR: P = 0.05, IRGC: P =0.2; 24 h: CEL: P = 0.001, IR: P = 0.004, IRGC: P = 0.3). Caspase-3, -8, and -9 activities were significantly reduced in neutrophils isolated after surgery and cultured for 12 h in IR horses, but not IRGC horses (IR caspase-3: P = 0.002, IR caspase-8: 0.002 P =, IR caspase-9: P = 0.04). Serum TNF-α concentration were increased in IRGC horses for 6-18 h following jejunal ischemia. Following surgery, ex vivo equine neutrophil apoptosis was delayed via down-regulation of caspase activity, which was ameliorated by PIM depletion potentially via upregulation of TNF-α.

中文翻译：

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肺血管内巨噬细胞耗竭可挽救炎症引起的中性粒细胞凋亡

这项研究的目的是使用马的肠道缺血和再灌注损伤的实验模型确定肺血管内巨噬细胞耗竭对全身炎症和离体中性粒细胞凋亡的影响。从手术前后的马中分离出中性粒细胞，将其随机分为3个治疗组：假体切开术（CEL，n = 4），肠缺血和再灌注（IR，n = 6），肠缺血和再灌注氯化g治疗以消耗肺血管内巨噬细胞（PIM，IRGC，n = 6）。用膜联蛋白V评估中性粒细胞的凋亡，并用流式细胞仪和中性粒细胞溶解产物中的caspase-3，-8和-9活性对碘化丙啶染色进行定量。手术后，所有马匹均发生全身性炎症反应。手术后 培养12或24小时后，体外中性粒细胞凋亡显着延迟，但IRGC马除外（12 h：CEL：P = 0.03，IR：P = 0.05，IRGC：P = 0.2; 24 h：CEL：P = 0.001， IR：P ＝ 0.004，IRGC：P ＝ 0.3）。手术后分离并在IR马中培养12 h的嗜中性白细胞中Caspase-3，-8和-9活性显着降低，但在IRGC马中培养12 h（IR caspase-3：P = 0.002，IR caspase-8：0.002 P = ，IR caspase-9：P ＝ 0.04）。空肠缺血后6至18小时，IRGC马的血清TNF-α浓度升高。手术后，离体马中性粒细胞凋亡通过下调caspase活性而延迟，这可能通过PIM耗竭而可能通过TNF-α上调而得到改善。P = 0.001，IR：P = 0.004，IRGC：P = 0.3）。手术后分离并在IR马中培养12 h的嗜中性白细胞中Caspase-3，-8和-9活性显着降低，但在IRGC马中培养12 h（IR caspase-3：P = 0.002，IR caspase-8：0.002 P = ，IR caspase-9：P ＝ 0.04）。空肠缺血后6至18小时，IRGC马的血清TNF-α浓度升高。手术后，离体马中性粒细胞凋亡通过下调caspase活性而延迟，这可能通过PIM耗竭而可能通过TNF-α上调而得到改善。P = 0.001，IR：P = 0.004，IRGC：P = 0.3）。手术后分离并在IR马中培养12 h的嗜中性白细胞中Caspase-3，-8和-9的活性显着降低，但IRGC马中没有培养（IR caspase-3：P = 0.002，IR caspase-8：0.002 P = ，IR caspase-9：P ＝ 0.04）。空肠缺血后6至18小时，IRGC马的血清TNF-α浓度升高。手术后，离体马中性粒细胞凋亡通过下调caspase活性而延迟，这可能通过PIM耗竭而可能通过TNF-α上调而得到改善。空肠缺血后6至18小时，IRGC马的血清TNF-α浓度升高。手术后，离体马中性粒细胞凋亡通过下调caspase活性而延迟，这可能通过PIM耗竭而可能通过TNF-α上调而得到改善。空肠缺血后6至18小时，IRGC马的血清TNF-α浓度升高。手术后，离体马中性粒细胞凋亡通过下调caspase活性而延迟，这可能通过PIM耗竭而可能通过TNF-α上调而得到改善。