Compartment-Specific Differences in the Activation of Monocyte Subpopulations Are Not Affected by Nitric Oxide and Glucocorticoid Treatment in a Model of Resuscitated Porcine Endotoxemic Shock

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.

Automated summary

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.