- Title
- Aim2 suppresses cigarette smoke-induced neutrophil recruitment, neutrophil caspase-1 activation and anti-Ly6G-mediated neutrophil depletion
- Creator
- Donovan, Chantal; Kim, Richard Y; Khan, Haroon; Pickles, Sophie; Sahu, Priyanka; Chimankar, Vrushali; Tu, Xiaofan; Ali, Md Khadem; Mayall, Jemma R.; Nguyen, Duc H.; Budden, Kurtis F.; Kumar, Vinod; Galvao, Izabela; Wark, Peter A. B.; Horvat, Jay C.; Hansbro, Philip M.; Ab Wark, P; Oliver, BG; Horvat, JC; Hansbro, PM; Jarnicki, Andrew G.; Brown, Alexandra C.; Jones-Freeman, Bernadette; Gomez, Henry M.; Wadhwa, Ridhima; Hortle, Elinor; Jayaraman, Ranjith
- Relation
- NHMRC.1120152 http://purl.org/au-research/grants/nhmrc/1120152 & 1138402 http://purl.org/au-research/grants/nhmrc/1138402 & 1079187 http://purl.org/au-research/grants/nhmrc/1079187 & 1120252 http://purl.org/au-research/grants/nhmrc/1120252
- Relation
- Immunology and Cell Biology Vol. 100, Issue 4, p. 235-249
- Publisher Link
- http://dx.doi.org/10.1111/imcb.12537
- Publisher
- John Wiley & Sons
- Resource Type
- journal article
- Date
- 2022
- Description
- Increased inflammasome responses are strongly implicated in inflammatory diseases; however, their specific roles are incompletely understood. Therefore, we sought to examine the roles of nucleotide-binding oligomerization domain–like receptor (NLR) family, pyrin domain–containing 3 (NLRP3) and absent in melanoma-2 (AIM2) inflammasomes in cigarette smoke–induced inflammation in a model of experimental chronic obstructive pulmonary disease (COPD). We targeted NLRP3 with the inhibitor MCC950 given prophylactically or therapeutically and examined Aim2−/− mice in cigarette smoke–induced experimental COPD. MCC950 treatment had minimal effects on disease development and/or progression. Aim2−/− mice had increased airway neutrophils with decreased caspase-1 levels, independent of changes in lung neutrophil chemokines. Suppressing neutrophils with anti-Ly6G in experimental COPD in wild-type mice reduced neutrophils in bone marrow, blood and lung. By contrast, anti-Ly6G treatment in Aim2−/− mice with experimental COPD had no effect on neutrophils in bone marrow, partially reduced neutrophils in the blood and had no effect on neutrophils or neutrophil caspase-1 levels in the lungs. These findings identify that following cigarette smoke exposure, Aim2 is important for anti-Ly6G–mediated depletion of neutrophils, suppression of neutrophil recruitment and mediates activation of caspase-1 in neutrophils.
- Subject
- Aim2; anti-Ly6G; cigarette smoke; inflammasome; lung; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1464489
- Identifier
- uon:47013
- Identifier
- ISSN:0818-9641
- Language
- eng
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