Abstract
BackgroundCarbonaceous nanoparticles possess an emerging source of human exposure due to the massive release of combustion products and the ongoing revolution in nanotechnology. Pulmonary inflammation caused by deposited nanoparticles is central for their adverse health effects. Epidemiological studies suggest that individuals with favourable lung physiology are at lower risk for particulate matter associated respiratory diseases probably due to efficient control of inflammation and repair process. Therefore we selected a mouse strain C3H/HeJ (C3) with robust lung physiology and exposed it to moderately toxic carbon nanoparticles (CNP) to study the elicited pulmonary inflammation and its resolution.Methods5 μg, 20 μg and 50 μg CNP were intratracheally (i.t.) instilled in C3 mice to identify the optimal dose for subsequent time course studies. Pulmonary inflammation was assessed using histology, bronchoalveolar lavage (BAL) analysis and by a panel of 62 protein markers.Results1 day after instillation of CNP, C3 mice exhibited a typical dose response, with the lowest dose (5 μg) representing the 'no effect level' as reflected by polymorphonuclear leucocyte (PMN), and BAL/lung concentrations of pro-inflammatory proteins. Histological analysis and BAL-protein concentration did not reveal any evidence of tissue injury in 20 μg CNP instilled animals. Accordingly time course assessment of the inflammatory response was performed after 3 and 7 days with this dose (20 μg). Compared to day 1, BAL PMN counts were significantly decreased at day 3 and completely returned to normal by day 7. We have identified protein markers related to the acute response and also to the time dependent response in lung and BAL. After complete resolution of PMN influx on day 7, we detected elevated concentrations of 20 markers that included IL1B, IL18, FGF2, EDN1, and VEGF in lung and/or BAL. Biological pathway analysis revealed these factors to be involved in a closely regulated molecular cascade with IL1B/IL18 as upstream and FGF2/EDN1/VEGF as downstream molecules.ConclusionConsidering the role of VEGF, FGF2 and EDN1 in lung development and morphogenesis together with the lack of any evident tissue damage we suggest a protective/homeostatic machinery to be associated in lungs of stable organisms to counter the CNP challenge as a precautionary measure.
Highlights
Various epidemiological and clinical studies have shown the correlation between ambient air particle concentration and adverse respiratory health effects throughout the industrialized world [1,2,3]
Considering the role of vascular endothelial growth factor (VEGF), FGF2 and EDN1 in lung development and morphogenesis together with the lack of any evident tissue damage we suggest a protective/ homeostatic machinery to be associated in lungs of stable organisms to counter the carbon nanoparticles (CNP) challenge as a precautionary measure
It is considered that individuals with impaired lung physiology are at higher risk to various respiratory diseases like chronic obstructive pulmonary disease (COPD) which are accelerated due to chronic exposure to environmental stressors like ultrafine particles/nano particles [4,5,6]
Summary
Various epidemiological and clinical studies have shown the correlation between ambient air particle concentration and adverse respiratory health effects throughout the industrialized world [1,2,3]. Individuals having a favorable lung physiology are considered to be at lower risk to various obstructive lung diseases probably due to efficient control of inflammatory and/repair processes. The pulmonary deposition efficiency of inhaled sub-100 nm particles, along with their large surface areas, is considered to be important in driving the emerging health effects linked to respiratory toxicity [8,9]. Epidemiological studies suggest that individuals with favourable lung physiology are at lower risk for particulate matter associated respiratory diseases probably due to efficient control of inflammation and repair process. We selected a mouse strain C3H/HeJ (C3) with robust lung physiology and exposed it to moderately toxic carbon nanoparticles (CNP) to study the elicited pulmonary inflammation and its resolution
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