Inflammasome Adaptor ASC Is Highly Elevated in Lung Over Plasma and Relates to Inflammation and Lung Diffusion in the Absence of Speck Formation
Rationale: Caspase-1 is a zymogen whose activation predominantly depends upon the assembly of ASC monomers into insoluble prion-like polymers (specks). ASC polymers support caspase-1 dimer formation inducing a proximity mediated auto-activation of caspase-1. Therefore, the amount and nature of ASC m...
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Frontiers Media S.A.
2020-03-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00461/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mikhail A. Gavrilin Mikhail A. Gavrilin Christian C. McAndrew Evan R. Prather Evan R. Prather MuChun Tsai MuChun Tsai Carleen R. Spitzer Carleen R. Spitzer Min-Ae Song Min-Ae Song Srabani Mitra Srabani Mitra Anasuya Sarkar Anasuya Sarkar Peter G. Shields Philip T. Diaz Philip T. Diaz Mark D. Wewers Mark D. Wewers |
spellingShingle |
Mikhail A. Gavrilin Mikhail A. Gavrilin Christian C. McAndrew Evan R. Prather Evan R. Prather MuChun Tsai MuChun Tsai Carleen R. Spitzer Carleen R. Spitzer Min-Ae Song Min-Ae Song Srabani Mitra Srabani Mitra Anasuya Sarkar Anasuya Sarkar Peter G. Shields Philip T. Diaz Philip T. Diaz Mark D. Wewers Mark D. Wewers Inflammasome Adaptor ASC Is Highly Elevated in Lung Over Plasma and Relates to Inflammation and Lung Diffusion in the Absence of Speck Formation Frontiers in Immunology bronchoalveolar lavage macrophages inflammasomes lung ASC smoking |
author_facet |
Mikhail A. Gavrilin Mikhail A. Gavrilin Christian C. McAndrew Evan R. Prather Evan R. Prather MuChun Tsai MuChun Tsai Carleen R. Spitzer Carleen R. Spitzer Min-Ae Song Min-Ae Song Srabani Mitra Srabani Mitra Anasuya Sarkar Anasuya Sarkar Peter G. Shields Philip T. Diaz Philip T. Diaz Mark D. Wewers Mark D. Wewers |
author_sort |
Mikhail A. Gavrilin |
title |
Inflammasome Adaptor ASC Is Highly Elevated in Lung Over Plasma and Relates to Inflammation and Lung Diffusion in the Absence of Speck Formation |
title_short |
Inflammasome Adaptor ASC Is Highly Elevated in Lung Over Plasma and Relates to Inflammation and Lung Diffusion in the Absence of Speck Formation |
title_full |
Inflammasome Adaptor ASC Is Highly Elevated in Lung Over Plasma and Relates to Inflammation and Lung Diffusion in the Absence of Speck Formation |
title_fullStr |
Inflammasome Adaptor ASC Is Highly Elevated in Lung Over Plasma and Relates to Inflammation and Lung Diffusion in the Absence of Speck Formation |
title_full_unstemmed |
Inflammasome Adaptor ASC Is Highly Elevated in Lung Over Plasma and Relates to Inflammation and Lung Diffusion in the Absence of Speck Formation |
title_sort |
inflammasome adaptor asc is highly elevated in lung over plasma and relates to inflammation and lung diffusion in the absence of speck formation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-03-01 |
description |
Rationale: Caspase-1 is a zymogen whose activation predominantly depends upon the assembly of ASC monomers into insoluble prion-like polymers (specks). ASC polymers support caspase-1 dimer formation inducing a proximity mediated auto-activation of caspase-1. Therefore, the amount and nature of ASC monomers and polymers in lung bronchoalveolar lavage fluid (BALF) might serve as a marker of lung inflammasome activity.Objectives: To determine whether lung ASC concentrations or oligomerization status predicts lung function or activity of lung inflammation.Methods: BALF ASC amount and oligomerization status was studied in three distinct cohorts: (1) young healthy non-smokers, vapers and smokers; (2) healthy HIV+ smokers who underwent detailed lung function studies; and (3) hospitalized patients with suspected pneumonia. We quantified cell free BALF ASC levels by ELISA and immunoblot. Oligomers (i.e., ASC specks) were identified by chemical crosslinking and ability to sediment with centrifugation.Measurement and Main Results: ASC levels are significantly higher in lung lining fluid than in plasma as well as higher in smoker lungs compared to non-smoker lungs. In this context, ASC levels correlate with macrophage numbers, smoking intensity and loss of lung diffusion capacity in a well-characterized cohort of healthy HIV+ smokers. However, only monomeric ASC was found in our BALF samples from all subjects, including patients with lung infections.Conclusions: Even though, most, if not all, extracellular ASC in BALF exists in the soluble, monomeric form, monomeric ASC concentrations still reflect the inflammatory status of the lung microenvironment and correlate with loss of lung function. |
topic |
bronchoalveolar lavage macrophages inflammasomes lung ASC smoking |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.00461/full |
work_keys_str_mv |
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doaj-1d59a9fb897c418a97241b94182ae7902020-11-25T02:40:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-03-011110.3389/fimmu.2020.00461530921Inflammasome Adaptor ASC Is Highly Elevated in Lung Over Plasma and Relates to Inflammation and Lung Diffusion in the Absence of Speck FormationMikhail A. Gavrilin0Mikhail A. Gavrilin1Christian C. McAndrew2Evan R. Prather3Evan R. Prather4MuChun Tsai5MuChun Tsai6Carleen R. Spitzer7Carleen R. Spitzer8Min-Ae Song9Min-Ae Song10Srabani Mitra11Srabani Mitra12Anasuya Sarkar13Anasuya Sarkar14Peter G. Shields15Philip T. Diaz16Philip T. Diaz17Mark D. Wewers18Mark D. Wewers19Pulmonary, Critical Care and Sleep Medicine Division, Department of Internal Medicine, The Ohio State University, Columbus, OH, United StatesDavis Heart and Lung Research Institute, Ohio State University, Columbus, OH, United StatesDavis Heart and Lung Research Institute, Ohio State University, Columbus, OH, United StatesPulmonary, Critical Care and Sleep Medicine Division, Department of Internal Medicine, The Ohio State University, Columbus, OH, United StatesDavis Heart and Lung Research Institute, Ohio State University, Columbus, OH, United StatesPulmonary, Critical Care and Sleep Medicine Division, Department of Internal Medicine, The Ohio State University, Columbus, OH, United StatesDavis Heart and Lung Research Institute, Ohio State University, Columbus, OH, United StatesPulmonary, Critical Care and Sleep Medicine Division, Department of Internal Medicine, The Ohio State University, Columbus, OH, United StatesDavis Heart and Lung Research Institute, Ohio State University, Columbus, OH, United StatesCollege of Public Health, The Ohio State University, Columbus, OH, United StatesComprehensive Cancer Center, James Cancer Hospital, The Ohio State University, Columbus, OH, United StatesPulmonary, Critical Care and Sleep Medicine Division, Department of Internal Medicine, The Ohio State University, Columbus, OH, United StatesDavis Heart and Lung Research Institute, Ohio State University, Columbus, OH, United StatesPulmonary, Critical Care and Sleep Medicine Division, Department of Internal Medicine, The Ohio State University, Columbus, OH, United StatesDavis Heart and Lung Research Institute, Ohio State University, Columbus, OH, United StatesComprehensive Cancer Center, James Cancer Hospital, The Ohio State University, Columbus, OH, United StatesPulmonary, Critical Care and Sleep Medicine Division, Department of Internal Medicine, The Ohio State University, Columbus, OH, United StatesDavis Heart and Lung Research Institute, Ohio State University, Columbus, OH, United StatesPulmonary, Critical Care and Sleep Medicine Division, Department of Internal Medicine, The Ohio State University, Columbus, OH, United StatesDavis Heart and Lung Research Institute, Ohio State University, Columbus, OH, United StatesRationale: Caspase-1 is a zymogen whose activation predominantly depends upon the assembly of ASC monomers into insoluble prion-like polymers (specks). ASC polymers support caspase-1 dimer formation inducing a proximity mediated auto-activation of caspase-1. Therefore, the amount and nature of ASC monomers and polymers in lung bronchoalveolar lavage fluid (BALF) might serve as a marker of lung inflammasome activity.Objectives: To determine whether lung ASC concentrations or oligomerization status predicts lung function or activity of lung inflammation.Methods: BALF ASC amount and oligomerization status was studied in three distinct cohorts: (1) young healthy non-smokers, vapers and smokers; (2) healthy HIV+ smokers who underwent detailed lung function studies; and (3) hospitalized patients with suspected pneumonia. We quantified cell free BALF ASC levels by ELISA and immunoblot. Oligomers (i.e., ASC specks) were identified by chemical crosslinking and ability to sediment with centrifugation.Measurement and Main Results: ASC levels are significantly higher in lung lining fluid than in plasma as well as higher in smoker lungs compared to non-smoker lungs. In this context, ASC levels correlate with macrophage numbers, smoking intensity and loss of lung diffusion capacity in a well-characterized cohort of healthy HIV+ smokers. However, only monomeric ASC was found in our BALF samples from all subjects, including patients with lung infections.Conclusions: Even though, most, if not all, extracellular ASC in BALF exists in the soluble, monomeric form, monomeric ASC concentrations still reflect the inflammatory status of the lung microenvironment and correlate with loss of lung function.https://www.frontiersin.org/article/10.3389/fimmu.2020.00461/fullbronchoalveolar lavagemacrophagesinflammasomeslungASCsmoking |