Home
|
Inbox
|
Search
|
View Abstract
CD163 Protects Against Ozone Increased Susceptibility to Bacterial Pneumonia
Description
.abstract img { width:300px !important; height:auto; display:block; text-align:center; margin-top:10px } .abstract { overflow-x:scroll } .abstract table { width:100%; display:block; border:hidden; border-collapse: collapse; margin-top:10px } .abstract td, th { border-top: 1px solid #ddd; padding: 4px 8px; } .abstract tbody tr:nth-child(even) td { background-color: #efefef; } .abstract a { overflow-wrap: break-word; word-wrap: break-word; }
A7556 - CD163 Protects Against Ozone Increased Susceptibility to Bacterial Pneumonia
Author Block: K. M. Gowdy1, S. W. Reece1, K. L. Cuddapah1, B. Kilburg-Basnyat1, C. Psaltis1, A. Hondros1, T. J. McMahon2, T. Zeczycki1, R. M. Tighe2; 1East Carolina University, Greenville, NC, United States, 2Duke Univ Med Ctr, Durham, NC, United States.
Background. Ozone (O3) exposure has been shown to increase susceptibility to pulmonary infections; however, the biological mechanisms are not well characterized. CD163 is a scavenger receptor exclusively expressed on monocytes and macrophages that is important in the clearance of cell free hemoglobin (CFH). Excessive CFH has recently been shown to increase lung injury and to decrease macrophage phagocytosis. Therefore, we hypothesize that CD163 is essential for clearance of O3-induced CFH and for maintenance of alveolar macrophage phagocytosis resulting in to sufficient respiratory pathogen clearance.
Methods. Male C57Bl/6J (CD163+/+) mice and CD163 deficient (CD163-/-) mice were exposed to filtered air (FA) or 1 ppm O3 for 3h. 24 hrs after exposure, mice were infected with 2000 cfus of Klebsiella pneumoniae (K. pneumoniae) by oropharyngeal aspiration. All mice were necropsied 24h post-infection and lung tissue and bronchoalveolar lavage (BAL) fluid were obtained. Lung tissue was homogenized and plated for bacterial quantification by colony forming units (cfus). Pulmonary inflammation was determined by BAL analysis of cytokine production and cellular differentials. Pulmonary injury was quantified by BAL protein and albumin.
Results. As previously reported, O3 enhanced pulmonary bacterial burden in CD163+/+ 24 hrs post-infection when compared to FA controls. CD163-/- mice exposed to FA did not have a difference in pulmonary bacterial burden compared to FA exposed CD163+/+ mice. However, 24h post K. pneumoniae infection, there was an increase in total cfus in the lungs of O3-exposed CD163-/- mice compared to CD163 sufficient controls exposed to O3. This increase in bacterial burden was associated with a significant increase in airspace neutrophilia as well as a slight increase in BAL macrophages.
Conclusions. This data demonstrates that CD163 plays an important role in protecting the lung from O3-induced susceptibility to bacterial pneumonia. The significant increase in levels of neutrophilia and macrophages found in CD163-/- mice compared to CD163+/+ mice demonstrates the role that CD163 has in preventing pulmonary injury post O3-exposure and bacterial infection. Future studies will focus on whether this phenotype is the result of impaired CFH clearance and/or macrophage phagocytosis.
Author Block: K. M. Gowdy1, S. W. Reece1, K. L. Cuddapah1, B. Kilburg-Basnyat1, C. Psaltis1, A. Hondros1, T. J. McMahon2, T. Zeczycki1, R. M. Tighe2; 1East Carolina University, Greenville, NC, United States, 2Duke Univ Med Ctr, Durham, NC, United States.
Background. Ozone (O3) exposure has been shown to increase susceptibility to pulmonary infections; however, the biological mechanisms are not well characterized. CD163 is a scavenger receptor exclusively expressed on monocytes and macrophages that is important in the clearance of cell free hemoglobin (CFH). Excessive CFH has recently been shown to increase lung injury and to decrease macrophage phagocytosis. Therefore, we hypothesize that CD163 is essential for clearance of O3-induced CFH and for maintenance of alveolar macrophage phagocytosis resulting in to sufficient respiratory pathogen clearance.
Methods. Male C57Bl/6J (CD163+/+) mice and CD163 deficient (CD163-/-) mice were exposed to filtered air (FA) or 1 ppm O3 for 3h. 24 hrs after exposure, mice were infected with 2000 cfus of Klebsiella pneumoniae (K. pneumoniae) by oropharyngeal aspiration. All mice were necropsied 24h post-infection and lung tissue and bronchoalveolar lavage (BAL) fluid were obtained. Lung tissue was homogenized and plated for bacterial quantification by colony forming units (cfus). Pulmonary inflammation was determined by BAL analysis of cytokine production and cellular differentials. Pulmonary injury was quantified by BAL protein and albumin.
Results. As previously reported, O3 enhanced pulmonary bacterial burden in CD163+/+ 24 hrs post-infection when compared to FA controls. CD163-/- mice exposed to FA did not have a difference in pulmonary bacterial burden compared to FA exposed CD163+/+ mice. However, 24h post K. pneumoniae infection, there was an increase in total cfus in the lungs of O3-exposed CD163-/- mice compared to CD163 sufficient controls exposed to O3. This increase in bacterial burden was associated with a significant increase in airspace neutrophilia as well as a slight increase in BAL macrophages.
Conclusions. This data demonstrates that CD163 plays an important role in protecting the lung from O3-induced susceptibility to bacterial pneumonia. The significant increase in levels of neutrophilia and macrophages found in CD163-/- mice compared to CD163+/+ mice demonstrates the role that CD163 has in preventing pulmonary injury post O3-exposure and bacterial infection. Future studies will focus on whether this phenotype is the result of impaired CFH clearance and/or macrophage phagocytosis.
|
Home
|
Inbox
|
Search
|