Milano Summer Particulate Matter (PM10) Triggers Lung Inflammation and Extra Pulmonary Adverse Events in Mice

Abstract

Recent studies have suggested a link between particulate matter (PM) exposure and increased mortality and morbidity associated with pulmonary and cardiovascular diseases; accumulating evidences point to a new role for air pollution in CNS diseases. The purpose of our study is to investigate PM10sum effects on lungs and extra pulmonary tissues. Milano PM10sum has been intratracheally instilled into BALB/c mice. Broncho Alveolar Lavage fluid, lung parenchyma, heart and brain were screened for markers of inflammation (cell counts, cytokines, ET-1, HO-1, MPO, iNOS), cytotoxicity (LDH, ALP, Hsp70, Caspase8-p18, Caspase3-p17) for a putative pro-carcinogenic marker (Cyp1B1) and for TLR4 pathway activation. Brain was also investigated for CD68, TNF-α, GFAP. In blood, cell counts were performed while plasma was screened for endothelial activation (sP-selectin, ET-1) and for inflammation markers (TNF-α, MIP-2, IL-1β, MPO). Genes up-regulation (HMOX1, Cyp1B1, IL-1β, MIP-2, MPO) and miR-21 have been investigated in lungs and blood. Inflammation in the respiratory tract of PM10sum-treated mice has been confirmed in BALf and lung parenchyma by increased PMNs percentage, increased ET-1, MPO and cytokines levels. A systemic spreading of lung inflammation in PM10sum-treated mice has been related to the increased blood total cell count and neutrophils percentage, as well as to increased blood MPO. The blood-endothelium interface activation has been confirmed by significant increases of plasma ET-1 and sP-selectin. Furthermore PM10sum induced heart endothelial activation and PAHs metabolism, proved by increased ET-1 and Cyp1B1 levels. Moreover, PM10sum causes an increase in brain HO-1 and ET-1. These results state the translocation of inflammation mediators, ultrafine particles, LPS, metals associated to PM10sum, from lungs to bloodstream, thus triggering a systemic reaction, mainly involving heart and brain. Our results provided additional insight into the toxicity of PM10sum and could facilitate shedding light on mechanisms underlying the development of urban air pollution related diseases.

Repeated Intratracheal Instillation of PM10 Induces Lipid Reshaping in Lung Parenchyma and in Extra-Pulmonary Tissues

“…In particular we previously recorded an increase of AMs and PMNs cells, mainly neutrophils, in BALF and blood of PM10sum treated mice [24].…”

“…Indeed, after PM10sum intratracheal instillation, we demonstrated an increase in inflammatory and coagulation markers in blood and heart tissue, and a concomitant increase in markers of brain blood barrier (BBB) damage as well as oxidative stress in brain parenchyma [24].…”

Impact of the Airborne Particulate Matter onthe Human Health

“…Inflammation in the respiratory tract of PM 10 -treated mice has been evidenced in BALf and lung parenchyma by increase of defense cells and cytokine levels. Farina et al (2013). )…”

“…The macrophages are several times more potent in producing proinflammatory mediators that contribute to the local inflammatory response; moreover they promote also the subsequent systemic inflammatory response (Hogg and Van Eeden, 2009). Recently different sized PM collected in a very polluted city and their effects on mice lungs and extra pulmonary tissues have been investigated (Figure 10.4; Table 10.4) (Farina et al, 2013).…”

“…In vitro studies have demonstrated a clear link between the biological actions of PM and levels of free radicals (Longhin et al, 2013). In vivo studies consistently find evidence for increased levels of oxidative stress in PM-exposed animals (Farina et al, 2013). At present it is unclear if particle-derived oxidative stress mediates the CV actions of inhaled particles.…”