Cardiopulmonary Bypass Induces Recruitment of Bone Marrow-Derived Leukocytes to the Lungs in Monkeys

Cardiopulmonary Bypass Induces Recruitment of Bone Marrow-Derived Leukocytes to the Lungs in Monkeys
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DOI:
10.1016/j.athoracsur.2013.10.072
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发表时间:
2014-02-01
影响因子:
4.6
通讯作者:
Sakakibara, Yuzuru
Sakakibara, Yuzuru
中科院分区:
医学2区
文献类型:
--
作者:
Goto, Yukinobu;Hiramatsu, Yuji;Sakakibara, Yuzuru

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背景资料。体外循环(CPB)引起的骨髓反应是一种全身性炎症反应,已被认为是一种全身性炎症反应,但尚未阐明。新释放的骨髓中的多形核白细胞(PMN)和单核细胞是已知的未成熟细胞,表明它们更有可能损害组织。本研究旨在研究非人类灵长类动物模型中与体外循环相关的骨髓来源的白细胞的动力学。通过正中胸骨切开对食蟹猴进行常温CPB 2小时。通过静脉注射5-溴-2‘-脱氧尿嘧啶核苷(BrdU)在猴体内标记白细胞前体,并用流式细胞术随时间监测白细胞前体在体外循环中的释放和术后重新聚集到肺中(对照组)。在正常状态下,BrdU标记的中性粒细胞(PMNBrdU)通过骨髓的时间为143.6+/-4.5h,单核细胞为100.9+/-7.6h。体外循环使中性粒细胞和单核细胞迅速从骨髓中释放出来,使它们在骨髓中的转运时间分别缩短到92.0+/-4.1和60.3+/-2.9小时,并进一步增加了它们在肺泡腔的出现,24小时后支气管肺泡灌洗液中IL-6和IL-8水平均显著升高。在我们的猴模型中,CPB加速了中性粒细胞和单核细胞从骨髓中释放并重新聚集到肺中,这表明该模型对于监测人类骨髓来源的白细胞的动力学是相关的。(C)2014年,由胸外科医生学会主办
Background. A bone marrow (BM) response induced by cardiopulmonary bypass (CPB) as a systemic inflammatory reaction has previously been postulated but not clarified. Newly released polymorphonuclear leukocytes (PMNs) and monocytes from the BM are known to be immature, indicating their greater potential to damage tissue. The present study aimed to examine the kinetics of BM-derived leukocytes associated with CPB in a nonhuman primate model.Methods. Normothermic CPB was performed in cynomolgus monkeys for 2 hours through a median sternotomy. Leukocyte precursors were labeled in the BM of the monkeys in vivo by an intravenous injection of 5-bromo-2'-deoxyuridine (BrdU), and their release into the circulation and recruitment to the lungs after operation with or without CPB (control group) were monitored over time by flow cytometry.Results. In normal-state monkeys, the calculated transit time of BrdU-labeled PMNs (PMNBrdU) through the BM was 143.6 +/- 4.5 hours and that of monocytes was 100.9 +/- 7.6 hours. CPB caused a rapid release of PMNs and monocytes from the BM, shortened their transit through the BM to 92.0 +/- 4.1 and 60.3 +/- 2.9 hours, respectively, and further induced their increased appearance in the alveolar spaces, with a significant increase in both interleukin (IL)-6 and IL-8 levels in the bronchoalveolar lavage fluid (BALF) 24 hours after CPB.Conclusions. CPB accelerated the release of PMNs and monocytes from the BM and their recruitment to the lungs in our monkey model, indicating that this model is relevant for monitoring the kinetics of BM-derived leukocytes in humans. (C) 2014 by The Society of Thoracic Surgeons