Research Article: Conversion from resistance to susceptibility: a dirty trick by PM 10
Abstract:
The results of whole-body exposure to airborne particulate matter <10?µm on the cornea of BALB/c mice, how their natural resistance to Pseudomonas aeruginosa (PA) keratitis is impacted, and whether plastoquinonyl-decyl-triphenylphosphonium (SKQ1) is protective were examined. Control or PM 10 exposure was performed for 2 weeks; corneal sensitivity, tear production, and Langerhans cell (LC) number were determined; and reverse transcription PCR (RT-PCR) was performed. After exposure, infection with PA, and topical treatment with PBS or SKQ1, clinical score, slit lamp, polymorphonuclear cells (PMN) quantitation, bacterial count, RT-PCR, Western blot, and flow cytometry were performed. PM 10 -exposed corneas showed significantly increased corneal sensitivity, decreased tear production, and a significant increase in conjunctival LC vs. control exposed eyes. PM 10 exposure significantly increased mRNA for proinflammatory cytokines and significantly decreased them for glutathione peroxidase 4 and Nrf2. Disease severity after PM 10 exposure was significantly increased at 3 and 5?dpi and resulted in higher plate counts and PMN numbers in the cornea at 5?dpi. Corneal mRNA levels after infection showed a similar pattern to the uninfected cornea after PM 10 exposure and were selectively confirmed by Western blot. Flow cytometry showed increases in macrophages and T cells in the cornea after infection following PM 10 exposure. SKQ1 significantly improved disease at both 3 and 5?dpi, restored mRNA and protein to control levels, reduced corneal bacteria and PMN number, and prevented increased sensitivity and tear reduction. Whole-body exposure to PM 10 resulted in converting BALB/c mice that exhibit genetic resistance to a susceptible phenotype in response to PA and SKQ1 reversed the majority of these effects and restored resistance.
Introduction:
Ambient air pollution, comprised of particulate matter (PM) (solid and liquid particles suspended in air) and gases, e.g., ozone, NO 2, and SO 2 , has reached unparalleled levels worldwide. Airborne particulate matter <10?µm in diameter (PM 10 ) is a significant environmental pollutant with well-documented effects on human health, with chronic exposure creating a serious challenge to public health. According to the World Health Organization, 92% of the world's population is affected by contaminated air,…
Read more