Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis*

Bélikova, Ioulia; Lukaszewicz, Anne Claire; Faivre, Valérie; Damoisel, Charles; Singer, Mervyn; Payen, Didier

doi:10.1097/01.ccm.0000295593.25106.c4

Cited by 102 publications

(102 citation statements)

References 34 publications

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“…In a recent study, we have also observed that mitochondrial function is altered in PBMCs following hemorrhagic shock and resuscitation in a rodent model (13). Similar to a report by Belikova et al (12), we found that PBMCs recovered mitochondrial function when incubated in serum from control animals with control PBMCs developed depressed function when incubated with serum collected following severe shock; suggesting a systemic factor may be responsible for mitochondrial dysfunction in PBMCs. However, the extent to which mitochondrial dysfunction in PBMCs parallels similar changes in other organ systems is not clear.…”

Section: Introductionsupporting

confidence: 91%

“…In particular, PBMC respiratory function may reflect disease severity in sepsis (12) and we have noted that PBMC mitochondrial function is dramatically altered during hemorrhagic shock and resuscitation (13). As such, monitoring PBMC respiratory capacity may provide a minimally invasive surrogate for end-organ mitochondrial function.…”

Section: Discussionmentioning

confidence: 99%

“…Secondly, we investigated the effects of hemorrhagic shock and resuscitation on mitochondrial function over a short duration. While isolated measurements of PBMC respiratory capacity may not reflect acute changes in tissue mitochondrial function following hemorrhagic shock, impaired PBMC mitochondrial function does appear to correlate with disease severity in other disease states such as sepsis (12). Longer term studies are need to determine if PBMC mitochondrial function following resuscitation can also be used to predict the development of MOF.…”

Section: Discussionmentioning

confidence: 99%

“…PBMC’s can be easily isolated following standard phlebotomy and provide a readily accessible tissue that can be repeatedly assayed during the course of resuscitation. In patients with sepsis, reduced oxygen consumption and lower mitochondrial membrane potential in PBMCs have been associated with disease severity, immune dysregulation, and decreased survival (11,12). In a recent study, we have also observed that mitochondrial function is altered in PBMCs following hemorrhagic shock and resuscitation in a rodent model (13).…”

Section: Introductionmentioning

confidence: 99%

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Can Peripheral Blood Mononuclear Cells Be Used as a Proxy for Mitochondrial Dysfunction in Vital Organs During Hemorrhagic Shock and Resuscitation?

Karamercan¹,

Weiss²,

Villarroel

et al. 2013

Shock

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INTRODUCTION Although mitochondrial dysfunction is thought to contribute to the development of post-traumatic organ failure, current techniques to assess mitochondrial function in tissues are invasive and clinically impractical. We hypothesized that mitochondrial function in peripheral blood mononuclear cells (PBMCs) would reflect cellular respiration in other organs during hemorrhagic shock and resuscitation (HS&R). METHODS Using a fixed pressure HS model, Long Evan’s rats were bled to a mean arterial pressure (MAP) of 40 mmHg. When blood pressure could no longer be sustained without intermittent fluid infusion (Decompensated HS), Lactated Ringer’s (LR) was incrementally infused to maintain the MAP at 40 mmHg until 40% of the shed blood volume was returned (Severe HS). Animals were then resuscitated with 4X total shed volume in LR over 60 minutes (Resuscitation). Control animals underwent the same surgical procedures, but were not hemorrhaged. Animals were randomized to Control (n=6), Decompensated HS (n=6), Severe HS (n=6) or Resuscitation (n=6) groups. Kidney, liver, and heart tissues as well as PBMC’s were harvested from animals in each group to measure mitochondrial oxygen consumption using high resolution respirometry. Flow cytometry was used to assess mitochondrial membrane potential (Ψm) in PBMCs. One-way ANOVA and Pearson correlations were performed. RESULTS Mitochondrial oxygen consumption decreased in all tissues, including PBMC’s, following Decompensated HS, Severe HS, and Resuscitation. However, the degree of impairment varied significantly across tissues during HS&R. Of the tissues investigated, PBMC mitochondrial oxygen consumption and Ψm provided the closest correlation to kidney mitochondrial function during HS (complex I: r =0.65; complex II: r=0.65; complex IV: r=0.52; p<0.05). This association, however, disappeared with resuscitation. A weaker association between PBMC and heart mitochondrial function was observed but no association was noted between PBMC and liver mitochondrial function. CONCLUSION All tissues including PBMC’s demonstrated significant mitochondrial dysfunction following HS&R. Although PBMC and kidney mitochondrial function correlated well during hemorrhagic shock, the variability in mitochondrial response across tissues over the spectrum of hemorrhagic shock and resuscitation limits the usefulness of using PBMC’s as a proxy for tissue-specific cellular respiration.

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Section: Introductionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Can Peripheral Blood Mononuclear Cells Be Used as a Proxy for Mitochondrial Dysfunction in Vital Organs During Hemorrhagic Shock and Resuscitation?

Karamercan¹,

Weiss²,

Villarroel

et al. 2013

Shock

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show abstract

“…Several investigations have demonstrated reduced function of different aspects of mitochondrial respiratory activity of peripheral blood immune cells (PBICs) in the early disease stages of sepsis patients admitted to the ICU [9-11]. The results are, however, somewhat divergent, probably reflecting differences in study population, experimental setup, and what mitochondria-specific markers have been chosen for normalization of respiration to cellular content of mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Patients with sepsis exhibit increased mitochondrial respiratory capacity in peripheral blood immune cells

et al. 2013

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IntroductionIn sepsis, mitochondria have been associated with both initial dysfunction and subsequent upregulation (biogenesis). However, the evolvement of mitochondrial function in sepsis over time is largely unknown, and we therefore investigated mitochondrial respiration in peripheral blood immune cells (PBICs) in sepsis patients during the first week after admission to the intensive care unit (ICU).MethodsPBICs from 20 patients with severe sepsis or septic shock were analyzed with high-resolution respirometry 3 times after admission to the ICU (within 48 hours, days 3 to 4 and days 6 to 7). Mitochondrial DNA (mtDNA), cytochrome c (Cyt c), and citrate synthase (CS) were measured as indicators of cellular mitochondrial content.ResultsIn intact PBICs with endogenous substrates, a gradual increase in cellular respiration reached 173% of controls after 1 week (P = 0.001). In permeabilized cells, respiration using substrates of complex I, II, and IV were significantly increased days 1 to 2, reaching 137%, 130%, and 173% of controls, respectively. In parallel, higher levels of CS activity, mtDNA, and Cyt c content in PBICs (211%, 243%, and 331% of controls for the respective indicators were found at days 6 to 7; P < 0.0001). No differences in respiratory capacities were noted between survivors and nonsurvivors at any of the time points measured.ConclusionsPBICs from patients with sepsis displayed higher mitochondrial respiratory capacities compared with controls, due to an increased mitochondrial content, as indicated by increased mitochondrial DNA, protein content, and enzyme activity. The results argue against mitochondrial respiratory dysfunction in this type of cells in sepsis.

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Resolvin E1 Improves Mitochondrial Function in Human Alveolar Epithelial Cells during Severe Inflammation

Mayer

Sommer

Hache

et al. 2019

Lipids

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Severe inflammatory disorders such as sepsis are a major cause of morbidity and mortality worldwide. Mitochondrial dysfunction is regarded as a key feature involved in inflammation pathogenesis. In the present study, we investigated the impact of the omega‐3 fatty acid‐derived lipid mediator Resolvin E1 (RvE1) on mitochondrial function in experimental pulmonary inflammation. RvE1 was found to exert anti‐inflammatory properties in human alveolar epithelial cells during severe inflammation. RvE1 is capable of restoring inflammation‐induced mitochondrial dysfunction and the impaired imbalance of mitochondrial fission and fusion. Experimental inhibition of mitochondrial fission with Mdivi‐1 in our model is associated with a significantly reduced inflammatory response and improved mitochondrial function. These findings suggest a novel functional mechanism for the beneficial effects of RvE1 in experimental pulmonary inflammatory reactions.

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Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis*

Abstract: Energetic failure of PBMCs in sepsis may be a factor associated with the modulation of immune response and human leukocyte antigen-DR phenotype, partially driven by plasma factors.

Cited by 102 publications

References 34 publications

Can Peripheral Blood Mononuclear Cells Be Used as a Proxy for Mitochondrial Dysfunction in Vital Organs During Hemorrhagic Shock and Resuscitation?

Can Peripheral Blood Mononuclear Cells Be Used as a Proxy for Mitochondrial Dysfunction in Vital Organs During Hemorrhagic Shock and Resuscitation?

Patients with sepsis exhibit increased mitochondrial respiratory capacity in peripheral blood immune cells

Resolvin E1 Improves Mitochondrial Function in Human Alveolar Epithelial Cells during Severe Inflammation

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