Effect of ultrafine particle matter on human peripheral blood mononuclear cells of chronic obstructive pulmonary disease patients: involvement of the inflammasome

Inflammation is central to the development of chronic obstructive pulmonary disease (COPD), caused by inhalation of noxious particles or gas, especially cigarette smoke (CS). Emerging genetic and pharmacological evidence suggests that IL-1-like cytokines are highly detected in the sputum and broncho-alveolar lavage (BAL) of COPD patients, implying the involvement of the multiprotein complex inflammasome. In order to understand the role of this complex in COPD, we isolated PBMCs from healthy volunteers (smoker and non-smoker) and COPD patients. To mimic environmental pollution, PBMCs were treated with ultrafine particulate matter (UFP, <50nm).We found that, differently from what already published on PBMCs from smokers treated with UFP, PBMCs from COPD patients were less susceptible to UFP treatment in terms of IL-1a, IL-1b and IL-18 release. This effect was also observed for the production of mitochondrial-derived reactive oxygen species, which were lower from PBMCs obtained from COPD patients than smokers, who presented higher levels of associated OGG1, involved in oxidative stress repair. In contrast, COPD-derived PBMCs treated with UFP had higher levels of IL-33 than healthy non smokers, similarly to what happened to smokers. Interestingly, IL-33 release in COPD patients was not caspase-1/8 dependent. In conclusion, our data imply that the inflammasome activation by UFP does not affect IL-18 release in COPD patients compared to healthy smokers. Moreover, caspase-1/8-independent release of IL-33 from PBMC from COPD after UFP exposure, opens new perspectives in the biology of the inflammasome in COPD patients.