The Experts below are selected from a list of 10776 Experts worldwide ranked by ideXlab platform
Peter H S Sporn - One of the best experts on this subject based on the ideXlab platform.
-
hypercapnia inhibits autophagy and bacterial killing in human macrophages by increasing expression of bcl 2 and bcl xl
Journal of Immunology, 2015Co-Authors: Marina S Casalinomatsuda, Aisha Nair, Greg J Beitel, Khalilah L Gates, Peter H S SpornAbstract:Hypercapnia, the elevation of CO 2 in blood and tissue, commonly develops in patients with advanced lung disease and severe pulmonary infections, and it is associated with high mortality. We previously reported that hypercapnia alters expression of host defense genes, inhibits phagocytosis, and increases the mortality of Pseudomonas Pneumonia in mice. However, the effect of hypercapnia on autophagy, a conserved process by which cells sequester and degrade proteins and damaged organelles that also plays a key role in antimicrobial host defense and pathogen clearance, has not previously been examined. In the present study we show that hypercapnia inhibits autophagy induced by starvation, rapamycin, LPS, heat-killed bacteria, and live bacteria in the human macrophage. Inhibition of autophagy by elevated CO 2 was not attributable to acidosis. Hypercapnia also reduced macrophage killing of Pseudomonas aeruginosa . Moreover, elevated CO 2 induced the expression of Bcl-2 and Bcl-xL, antiapoptotic factors that negatively regulate autophagy by blocking Beclin 1, an essential component of the autophagy initiation complex. Furthermore, small interfering RNA targeting Bcl-2 and Bcl-xL and the small molecule Z36, which blocks Bcl-2 and Bcl-xL binding to Beclin 1, prevented hypercapnic inhibition of autophagy and bacterial killing. These results suggest that targeting the Bcl-2/Bcl-xL–Beclin 1 interaction may hold promise for ameliorating hypercapnia-induced immunosuppression and improving resistance to infection in patients with advanced lung disease and hypercapnia.
-
hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas Pneumonia
American Journal of Respiratory Cell and Molecular Biology, 2013Co-Authors: Khalilah L Gates, Lynn C Welch, Aisha Nair, Greg J Beitel, Heather A Howell, Christine U Vohwinkel, Jacob I. Sznajder, Alan R. Hauser, Peter H S SpornAbstract: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% N2) on outcomes of Pseudomonas aeruginosa Pneumonia in BALB/c mice and on pulmonary neutrophil function. We found 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.
-
hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas Pneumonia
American Journal of Respiratory Cell and Molecular Biology, 2013Co-Authors: Khalilah L Gates, Lynn C Welch, Aisha Nair, Greg J Beitel, Heather A Howell, Christine U Vohwinkel, Jacob I. Sznajder, Alan R. Hauser, Peter H S SpornAbstract: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% N2) on outcomes of Pseudomonas aeruginosa Pneumonia in BALB/c mice and on pulmonary neutrophil function. We found 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.
Khalilah L Gates - One of the best experts on this subject based on the ideXlab platform.
-
hypercapnia inhibits autophagy and bacterial killing in human macrophages by increasing expression of bcl 2 and bcl xl
Journal of Immunology, 2015Co-Authors: Marina S Casalinomatsuda, Aisha Nair, Greg J Beitel, Khalilah L Gates, Peter H S SpornAbstract:Hypercapnia, the elevation of CO 2 in blood and tissue, commonly develops in patients with advanced lung disease and severe pulmonary infections, and it is associated with high mortality. We previously reported that hypercapnia alters expression of host defense genes, inhibits phagocytosis, and increases the mortality of Pseudomonas Pneumonia in mice. However, the effect of hypercapnia on autophagy, a conserved process by which cells sequester and degrade proteins and damaged organelles that also plays a key role in antimicrobial host defense and pathogen clearance, has not previously been examined. In the present study we show that hypercapnia inhibits autophagy induced by starvation, rapamycin, LPS, heat-killed bacteria, and live bacteria in the human macrophage. Inhibition of autophagy by elevated CO 2 was not attributable to acidosis. Hypercapnia also reduced macrophage killing of Pseudomonas aeruginosa . Moreover, elevated CO 2 induced the expression of Bcl-2 and Bcl-xL, antiapoptotic factors that negatively regulate autophagy by blocking Beclin 1, an essential component of the autophagy initiation complex. Furthermore, small interfering RNA targeting Bcl-2 and Bcl-xL and the small molecule Z36, which blocks Bcl-2 and Bcl-xL binding to Beclin 1, prevented hypercapnic inhibition of autophagy and bacterial killing. These results suggest that targeting the Bcl-2/Bcl-xL–Beclin 1 interaction may hold promise for ameliorating hypercapnia-induced immunosuppression and improving resistance to infection in patients with advanced lung disease and hypercapnia.
-
hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas Pneumonia
American Journal of Respiratory Cell and Molecular Biology, 2013Co-Authors: Khalilah L Gates, Lynn C Welch, Aisha Nair, Greg J Beitel, Heather A Howell, Christine U Vohwinkel, Jacob I. Sznajder, Alan R. Hauser, Peter H S SpornAbstract: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% N2) on outcomes of Pseudomonas aeruginosa Pneumonia in BALB/c mice and on pulmonary neutrophil function. We found 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.
-
hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas Pneumonia
American Journal of Respiratory Cell and Molecular Biology, 2013Co-Authors: Khalilah L Gates, Lynn C Welch, Aisha Nair, Greg J Beitel, Heather A Howell, Christine U Vohwinkel, Jacob I. Sznajder, Alan R. Hauser, Peter H S SpornAbstract: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% N2) on outcomes of Pseudomonas aeruginosa Pneumonia in BALB/c mice and on pulmonary neutrophil function. We found 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.
Aisha Nair - One of the best experts on this subject based on the ideXlab platform.
-
hypercapnia inhibits autophagy and bacterial killing in human macrophages by increasing expression of bcl 2 and bcl xl
Journal of Immunology, 2015Co-Authors: Marina S Casalinomatsuda, Aisha Nair, Greg J Beitel, Khalilah L Gates, Peter H S SpornAbstract:Hypercapnia, the elevation of CO 2 in blood and tissue, commonly develops in patients with advanced lung disease and severe pulmonary infections, and it is associated with high mortality. We previously reported that hypercapnia alters expression of host defense genes, inhibits phagocytosis, and increases the mortality of Pseudomonas Pneumonia in mice. However, the effect of hypercapnia on autophagy, a conserved process by which cells sequester and degrade proteins and damaged organelles that also plays a key role in antimicrobial host defense and pathogen clearance, has not previously been examined. In the present study we show that hypercapnia inhibits autophagy induced by starvation, rapamycin, LPS, heat-killed bacteria, and live bacteria in the human macrophage. Inhibition of autophagy by elevated CO 2 was not attributable to acidosis. Hypercapnia also reduced macrophage killing of Pseudomonas aeruginosa . Moreover, elevated CO 2 induced the expression of Bcl-2 and Bcl-xL, antiapoptotic factors that negatively regulate autophagy by blocking Beclin 1, an essential component of the autophagy initiation complex. Furthermore, small interfering RNA targeting Bcl-2 and Bcl-xL and the small molecule Z36, which blocks Bcl-2 and Bcl-xL binding to Beclin 1, prevented hypercapnic inhibition of autophagy and bacterial killing. These results suggest that targeting the Bcl-2/Bcl-xL–Beclin 1 interaction may hold promise for ameliorating hypercapnia-induced immunosuppression and improving resistance to infection in patients with advanced lung disease and hypercapnia.
-
hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas Pneumonia
American Journal of Respiratory Cell and Molecular Biology, 2013Co-Authors: Khalilah L Gates, Lynn C Welch, Aisha Nair, Greg J Beitel, Heather A Howell, Christine U Vohwinkel, Jacob I. Sznajder, Alan R. Hauser, Peter H S SpornAbstract: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% N2) on outcomes of Pseudomonas aeruginosa Pneumonia in BALB/c mice and on pulmonary neutrophil function. We found 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.
-
hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas Pneumonia
American Journal of Respiratory Cell and Molecular Biology, 2013Co-Authors: Khalilah L Gates, Lynn C Welch, Aisha Nair, Greg J Beitel, Heather A Howell, Christine U Vohwinkel, Jacob I. Sznajder, Alan R. Hauser, Peter H S SpornAbstract: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% N2) on outcomes of Pseudomonas aeruginosa Pneumonia in BALB/c mice and on pulmonary neutrophil function. We found 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.
Greg J Beitel - One of the best experts on this subject based on the ideXlab platform.
-
hypercapnia inhibits autophagy and bacterial killing in human macrophages by increasing expression of bcl 2 and bcl xl
Journal of Immunology, 2015Co-Authors: Marina S Casalinomatsuda, Aisha Nair, Greg J Beitel, Khalilah L Gates, Peter H S SpornAbstract:Hypercapnia, the elevation of CO 2 in blood and tissue, commonly develops in patients with advanced lung disease and severe pulmonary infections, and it is associated with high mortality. We previously reported that hypercapnia alters expression of host defense genes, inhibits phagocytosis, and increases the mortality of Pseudomonas Pneumonia in mice. However, the effect of hypercapnia on autophagy, a conserved process by which cells sequester and degrade proteins and damaged organelles that also plays a key role in antimicrobial host defense and pathogen clearance, has not previously been examined. In the present study we show that hypercapnia inhibits autophagy induced by starvation, rapamycin, LPS, heat-killed bacteria, and live bacteria in the human macrophage. Inhibition of autophagy by elevated CO 2 was not attributable to acidosis. Hypercapnia also reduced macrophage killing of Pseudomonas aeruginosa . Moreover, elevated CO 2 induced the expression of Bcl-2 and Bcl-xL, antiapoptotic factors that negatively regulate autophagy by blocking Beclin 1, an essential component of the autophagy initiation complex. Furthermore, small interfering RNA targeting Bcl-2 and Bcl-xL and the small molecule Z36, which blocks Bcl-2 and Bcl-xL binding to Beclin 1, prevented hypercapnic inhibition of autophagy and bacterial killing. These results suggest that targeting the Bcl-2/Bcl-xL–Beclin 1 interaction may hold promise for ameliorating hypercapnia-induced immunosuppression and improving resistance to infection in patients with advanced lung disease and hypercapnia.
-
hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas Pneumonia
American Journal of Respiratory Cell and Molecular Biology, 2013Co-Authors: Khalilah L Gates, Lynn C Welch, Aisha Nair, Greg J Beitel, Heather A Howell, Christine U Vohwinkel, Jacob I. Sznajder, Alan R. Hauser, Peter H S SpornAbstract: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% N2) on outcomes of Pseudomonas aeruginosa Pneumonia in BALB/c mice and on pulmonary neutrophil function. We found 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.
-
hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas Pneumonia
American Journal of Respiratory Cell and Molecular Biology, 2013Co-Authors: Khalilah L Gates, Lynn C Welch, Aisha Nair, Greg J Beitel, Heather A Howell, Christine U Vohwinkel, Jacob I. Sznajder, Alan R. Hauser, Peter H S SpornAbstract: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% N2) on outcomes of Pseudomonas aeruginosa Pneumonia in BALB/c mice and on pulmonary neutrophil function. We found 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.
Jacob I. Sznajder - One of the best experts on this subject based on the ideXlab platform.
-
hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas Pneumonia
American Journal of Respiratory Cell and Molecular Biology, 2013Co-Authors: Khalilah L Gates, Lynn C Welch, Aisha Nair, Greg J Beitel, Heather A Howell, Christine U Vohwinkel, Jacob I. Sznajder, Alan R. Hauser, Peter H S SpornAbstract: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% N2) on outcomes of Pseudomonas aeruginosa Pneumonia in BALB/c mice and on pulmonary neutrophil function. We found 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.
-
hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas Pneumonia
American Journal of Respiratory Cell and Molecular Biology, 2013Co-Authors: Khalilah L Gates, Lynn C Welch, Aisha Nair, Greg J Beitel, Heather A Howell, Christine U Vohwinkel, Jacob I. Sznajder, Alan R. Hauser, Peter H S SpornAbstract: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% N2) on outcomes of Pseudomonas aeruginosa Pneumonia in BALB/c mice and on pulmonary neutrophil function. We found 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.
