Hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas pneumonia

Khalilah L. Gates*, Heather A. Howell, Aisha Nair, Christine U. Vohwinkel, Lynn C. Welch, Greg J. Beitel, Alan R. Hauser, Jacob I. Sznajder, Peter H S Sporn

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Hypercapnia, an elevation of the level of carbon dioxide (CO2) in blood and tissues, is a marker of poor prognosis in chronic obstructive pulmonary disease and other pulmonary disorders. We previously reported that hypercapnia inhibits the expression of TNF and IL-6 and phagocytosis in macrophages in vitro. In the present study, we determined the effects of normoxic hypercapnia (10%CO2, 21% O2, and 69% N 2) on outcomes of Pseudomonas aeruginosa pneumonia in BALB/c mice and on pulmonary neutrophil function.Wefound that the mortality of P. aeruginosa pneumonia was increased in 10% CO2-exposed compared with air-exposed mice. Hypercapnia increased pneumonia mortality similarly in mice with acute and chronic respiratory acidosis, indicating an effect unrelated to the degree of acidosis. Exposure to 10% CO2 increased the burden of P. aeruginosa in the lungs, spleen, and liver, but did not alter lung injury attributable to pneumonia. Hypercapnia did not reduce pulmonary neutrophil recruitment during infection, but alveolar neutrophils from 10% CO2-exposed mice phagocytosed fewer bacteria and produced less H2O2 than neutrophils from air-exposed mice. Secretion of IL-6 and TNF in the lungs of 10% CO2-exposed mice was decreased 7 hours, but not 15 hours, after the onset of pneumonia, indicating that hypercapnia inhibited the early cytokine response to infection. The increase in pneumonia mortality caused by elevated CO2 was reversible when hypercapnic mice were returned to breathing air before or immediately after infection. These results suggest that hypercapnia may increase the susceptibility to and/or worsen the outcome of lung infections in patients with severe lung disease.

Original languageEnglish (US)
Pages (from-to)821-828
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume49
Issue number5
DOIs
StatePublished - Nov 1 2013

Fingerprint

Hypercapnia
Pseudomonas
Pneumonia
Pulmonary diseases
Neutrophils
Lung
Mortality
Interleukin-6
Air
Pseudomonas aeruginosa
Macrophages
Carbon Dioxide
Liver
Infection
Phagocytosis
Bacteria
Blood
Tissue
Cytokines
Respiratory Acidosis

Keywords

  • Carbon dioxide
  • Inflammation
  • Phagocytosis
  • Pulmonary infection
  • Reactive oxygen species

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

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title = "Hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas pneumonia",
abstract = "Hypercapnia, an elevation of the level of carbon dioxide (CO2) in blood and tissues, is a marker of poor prognosis in chronic obstructive pulmonary disease and other pulmonary disorders. We previously reported that hypercapnia inhibits the expression of TNF and IL-6 and phagocytosis in macrophages in vitro. In the present study, we determined the effects of normoxic hypercapnia (10{\%}CO2, 21{\%} O2, and 69{\%} N 2) on outcomes of Pseudomonas aeruginosa pneumonia in BALB/c mice and on pulmonary neutrophil function.Wefound that the mortality of P. aeruginosa pneumonia was increased in 10{\%} CO2-exposed compared with air-exposed mice. Hypercapnia increased pneumonia mortality similarly in mice with acute and chronic respiratory acidosis, indicating an effect unrelated to the degree of acidosis. Exposure to 10{\%} CO2 increased the burden of P. aeruginosa in the lungs, spleen, and liver, but did not alter lung injury attributable to pneumonia. Hypercapnia did not reduce pulmonary neutrophil recruitment during infection, but alveolar neutrophils from 10{\%} CO2-exposed mice phagocytosed fewer bacteria and produced less H2O2 than neutrophils from air-exposed mice. Secretion of IL-6 and TNF in the lungs of 10{\%} CO2-exposed mice was decreased 7 hours, but not 15 hours, after the onset of pneumonia, indicating that hypercapnia inhibited the early cytokine response to infection. The increase in pneumonia mortality caused by elevated CO2 was reversible when hypercapnic mice were returned to breathing air before or immediately after infection. These results suggest that hypercapnia may increase the susceptibility to and/or worsen the outcome of lung infections in patients with severe lung disease.",
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Hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas pneumonia. / Gates, Khalilah L.; Howell, Heather A.; Nair, Aisha; Vohwinkel, Christine U.; Welch, Lynn C.; Beitel, Greg J.; Hauser, Alan R.; Sznajder, Jacob I.; Sporn, Peter H S.

In: American journal of respiratory cell and molecular biology, Vol. 49, No. 5, 01.11.2013, p. 821-828.

Research output: Contribution to journalArticle

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T1 - Hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas pneumonia

AU - Gates, Khalilah L.

AU - Howell, Heather A.

AU - Nair, Aisha

AU - Vohwinkel, Christine U.

AU - Welch, Lynn C.

AU - Beitel, Greg J.

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AU - Sznajder, Jacob I.

AU - Sporn, Peter H S

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AB - Hypercapnia, an elevation of the level of carbon dioxide (CO2) in blood and tissues, is a marker of poor prognosis in chronic obstructive pulmonary disease and other pulmonary disorders. We previously reported that hypercapnia inhibits the expression of TNF and IL-6 and phagocytosis in macrophages in vitro. In the present study, we determined the effects of normoxic hypercapnia (10%CO2, 21% O2, and 69% N 2) on outcomes of Pseudomonas aeruginosa pneumonia in BALB/c mice and on pulmonary neutrophil function.Wefound that the mortality of P. aeruginosa pneumonia was increased in 10% CO2-exposed compared with air-exposed mice. Hypercapnia increased pneumonia mortality similarly in mice with acute and chronic respiratory acidosis, indicating an effect unrelated to the degree of acidosis. Exposure to 10% CO2 increased the burden of P. aeruginosa in the lungs, spleen, and liver, but did not alter lung injury attributable to pneumonia. Hypercapnia did not reduce pulmonary neutrophil recruitment during infection, but alveolar neutrophils from 10% CO2-exposed mice phagocytosed fewer bacteria and produced less H2O2 than neutrophils from air-exposed mice. Secretion of IL-6 and TNF in the lungs of 10% CO2-exposed mice was decreased 7 hours, but not 15 hours, after the onset of pneumonia, indicating that hypercapnia inhibited the early cytokine response to infection. The increase in pneumonia mortality caused by elevated CO2 was reversible when hypercapnic mice were returned to breathing air before or immediately after infection. These results suggest that hypercapnia may increase the susceptibility to and/or worsen the outcome of lung infections in patients with severe lung disease.

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KW - Reactive oxygen species

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