Atmospheric Particulate Matter Aggravates Asthma Airway Inflammation And Its Mechanism

Objective:Asthma is a chronic disease that characterized with airway hyperresponsiveness(AHR),inflammation and remodeling.So far,epidemiological data have revealed that the elevation of fine ambient particulate matter(aerodynamic diameter<2.5 μm;PM2.5)is closely associated with an exacerbation of asthma while the underlying mechanism is poorly understood.In this study,we aim to explore the possible mechanism.Methods:Using a murine model,we investigated the impact of PM2.5 instillation on the development of asthma.Prior to the challenge with OVA on day 14,mice were administrated with PM2.5,phosphate-buffer saline(PBS)or control filter extracts(CFE).The responsiveness to methacholine(MCh)aerosols and the bronchoalveolar lavage fluid(BALF)parameters were measured 48 h after the OVA challenge.The animal bronchoalveolar lavage fluid(BALF),blood,and lung tissue were collected for analysis.IL-33,IL-4,IL-13,Eotaxin-1 in BALF and OVA-specific IgE in the serum were measured by ELISA.Hematoxylin-eosin(H&E)was conducted to detect inflammatory cell infiltration.AM and IM were isolated,then M2 makers were measured by Confocal fluorescence microscopy and Western Boltting(WB).Polarized M2 macrophages were adoptively transferred into allergic mice after the last OVA challenge,the percentage of CD11b+Siglec+eosinophils in the lungs homogenates were analyzed by flow cytometry.In vitro study,the effect of PM2.5 on MH-S and BMDM cells were analyzed.The eotaxin-1 in the supernatants of polarized M2 were measured by ELISA.Results:Results showed that compared to PBS or CFE instillation,PM2.5 combined with OVA co-exposure led to higher airway hyperresponsiveness(AHR)and severer eosinophils infiltration.Both alveolar and interstitial macrophages are alternatively activated with a propensity to M2 marked by arginase-1,CD206,and YM-1 in OVA-challenged mice.PM2.5 instillation significantly upregulated YM-1 expression,implying aggravated polarization and recruitment of M2 macrophages.Eotaxin-1 was detected to predominantly distributed in YM-1-positive macrophages and its level as well as IgE,IL-4 or IL-13 were increased by PM2.5.With the induction of bone marrow-derived macrophages(BMDM)to M2 macrophages,polarized macrophages were adoptively transferred into allergic mice and an increase of CD11b+Siglec+eosinophils was observed in lungs.In addition,PM2.5 was also administered to BMDM in vitro while no significant polarization was found.Conclusions:Our findings suggested that PM 2.5 could dramatically exacerbate asthma,highlighting for the first time a potent contribution of eotaxin-1 released from M2 macrophages to the pathogenesis of this disorder.