LPS Response Is Impaired by Urban Fine Particulate Matter

Abstract

Fine particulate matter (PM2.5) is a complex mixture of components with diverse chemical and physical characteristics associated with increased respiratory and cardiovascular diseases mortality. Our study aimed to investigate the effects of exposure to concentrated PM2.5 on LPS-induced lung injury onset. BALB/c male mice were exposed to either filtered air or ambient fine PM2.5 in an ambient particle concentrator for 5 weeks. Then, an acute lung injury was induced with nebulized LPS. The animals were euthanized 24 h after the nebulization to either LPS or saline. Inflammatory cells and cytokines (IL-1β, IL-4, IL-5, IL-6, IL-10, IL-17, TNF) were assessed in the blood, bronchoalveolar lavage fluid (BALF), and lung tissue. In addition, lung morphology was assessed by stereological methods. Our results showed that the PM+LPS group showed histological evidence of injury, leukocytosis with increased neutrophils and macrophages, and a mixed inflammatory response profile, with increased KC, IL-6, IL-1β, IL-4, and IL-17. Our analysis shows that there is an interaction between the LPS nebulization and PM2.5 exposure, differently modulating the inflammatory response, with a distinct response pattern as compared to LPS or PM2.5 exposure alone. Further studies are required to explain the mechanism of immune modulation caused by PM2.5 exposure.

Vitamin D3 regulates PM-driven primary human neutrophil inflammatory responses

“…Moreover, these data would suggest that the contemporary PM2.5 sample from Chiang Mai is less immunostimulatory than the historic SRM 1648a. Our study suggests that preexposure to PM alters the response of human neutrophils stimulated by LPS, consistent with findings in a recent study using a mouse model 38 .…”

“…Our results revealed that PM increased IL-8, but reduced IL-8 receptor expression and migration in response to LPS stimulation. This is relevant to a previous study in a mouse model in which PM reduced neutrophil migration to the lungs in response to LPS by decreasing gene expression of TLR-4 and MyD88 38 . Moreover, TLR4-induced loss of IL-8 receptor (CXCR2) was modified by enhanced LPS presentation efficiency 43 .…”