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

Sjövall, Fredrik LU orcid ; Morota, Saori ; Persson, Johan LU ; Hansson, Magnus LU orcid and Elmer, Eskil LU orcid (2013) In Critical Care 17(4).
Abstract
Introduction: In 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). Methods: PBICs 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.... (More)
Introduction: In 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). Methods: PBICs 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. Results: In 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. Conclusions: PBICs 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. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Critical Care
volume
17
issue
4
article number
R152
publisher
BioMed Central (BMC)
external identifiers
  • wos:000331539700026
  • scopus:84880955082
  • pmid:23883738
ISSN
1364-8535
DOI
10.1186/cc12831
language
English
LU publication?
yes
id
155a4a87-0847-4014-ae39-0021a7ebfe12 (old id 4376608)
date added to LUP
2016-04-01 10:01:48
date last changed
2024-01-06 05:59:46
@article{155a4a87-0847-4014-ae39-0021a7ebfe12,
  abstract     = {{Introduction: In 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). Methods: PBICs 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. Results: In 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 &lt; 0.0001). No differences in respiratory capacities were noted between survivors and nonsurvivors at any of the time points measured. Conclusions: PBICs 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.}},
  author       = {{Sjövall, Fredrik and Morota, Saori and Persson, Johan and Hansson, Magnus and Elmer, Eskil}},
  issn         = {{1364-8535}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Critical Care}},
  title        = {{Patients with sepsis exhibit increased mitochondrial respiratory capacity in peripheral blood immune cells}},
  url          = {{https://lup.lub.lu.se/search/files/1491913/4646876}},
  doi          = {{10.1186/cc12831}},
  volume       = {{17}},
  year         = {{2013}},
}