Journal
JOURNAL OF CLINICAL MEDICINE
Volume 11, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/jcm11092641
Keywords
sepsis; porcine model; compartmentalization; innate immunity; shock; monocyte
Categories
Funding
- Claes Frostell Research and Consulting AB, Stockholm, Sweden
- Wroclaw Medical University (Poland) [SUB.Z.A170.22.073]
- National Science Centre [UMO-2016/23/D/NZ6/02554]
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This study investigated the effects of iNO and steroid treatment on monocyte subsets in a porcine model of endotoxemia. The results showed decreased SLA-DR expression and increased mitochondrial membrane potential in specific subsets of monocytes. The study also highlighted the importance of studying tissue-resident cells in addition to circulating counterparts.
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 (Delta phi) 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(+). Delta phi 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 Delta phi than PB and BM monocytes, while the Delta phi 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.
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