Skirecki Tomasz, Adamik Barbara, Frostell Claes, Pasławska Urszula, Zieliński Stanisław, Glatzel-Plucińska Natalia, Olbromski Mateusz, Dzięgiel Piotr, Gozdzik Waldemar
Laboratory of Flow Cytometry, Centre of Postgraduate Medical Education Marymoncka 99/103, 01-813 Warsaw, Poland.
Clinical Department of the Anaesthesiology and Intensive Therapy, Wroclaw Medical University, 50-367 Wroclaw, Poland.
J Clin Med. 2022 May 8;11(9):2641. doi: 10.3390/jcm11092641.
Inhaled nitric oxide (iNO) remains one of the treatment modalities in shock, and in addition to its vasoactive properties, iNO exerts immunomodulatory effects. We used a porcine model of endotoxemia with shock resuscitation (control) and additional treatment with iNO and a steroid (treatment group). After 20 h, bone marrow (BM), peripheral blood (PB), and bronchoalveolar lavage fluid (BALF) were collected to analyze the immunophenotype and mitochondrial membrane potential (Δφ) in three subsets of monocytes. In both groups, SLA-DR expression decreased twofold on the circulating CD14+CD163+ and CD14−CD163+ monocytes, while it did not change on the CD14+CD163+. Δφ increased only in the CD14−CD163+ subpopulation (0.8 vs. 2.0, p < 0.001). The analysis of compartment-specific alterations showed that nearly 100% of BALF CD14+CD163+ and CD14−CD163+ monocytes expressed SLA-DR, and it was higher compared to PB (32% and 20%, p < 0.0001) and BM (93% and 67%, p < 0.001, respectively) counterparts. BALF CD14+CD163+ had a threefold higher Δφ than PB and BM monocytes, while the Δφ of the other subsets was highest in PB monocytes. We confirmed the compartmentalization of the monocyte response during endotoxemic shock, which highlights the importance of studying tissue-resident cells in addition to their circulating counterparts. The iNO/steroid treatment did not further impair monocyte fitness.
吸入一氧化氮（iNO）仍是休克的治疗方式之一，除了具有血管活性特性外，iNO还具有免疫调节作用。我们使用了一个内毒素血症伴休克复苏的猪模型（对照组），并对其进行iNO和类固醇的额外治疗（治疗组）。20小时后，收集骨髓（BM）、外周血（PB）和支气管肺泡灌洗液（BALF），以分析单核细胞三个亚群中的免疫表型和线粒体膜电位（Δφ）。在两组中，循环中的CD14+CD163+和CD14−CD163+单核细胞上SLA-DR表达下降了两倍，而CD14+CD163+单核细胞上的SLA-DR表达没有变化。Δφ仅在CD14−CD163+亚群中增加（0.8对2.0，p<0.001）。对特定隔室变化的分析表明，几乎100%的BALF CD14+CD163+和CD14−CD163+单核细胞表达SLA-DR，与PB（分别为32%和20%，p<0.0001）和BM（分别为93%和67%，p<0.001）中的对应细胞相比更高。BALF CD14+CD163+的Δφ比PB和BM单核细胞高三倍，而其他亚群的Δφ在PB单核细胞中最高。我们证实了内毒素血症休克期间单核细胞反应的区室化，这突出了除循环对应细胞外研究组织驻留细胞的重要性。iNO/类固醇治疗并未进一步损害单核细胞的健康状况。
