Impaired resolution of inflammatory response in the lungs of JF1-Msf mice following carbon nanoparticle instillationReportar como inadecuado




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Respiratory Research

, 12:94

First Online: 01 December 2011Received: 07 May 2011Accepted: 15 July 2011

Abstract

BackgroundDeclined lung function is a risk factor for particulate matter associated respiratory diseases like asthma and chronic obstructive pulmonary disease COPD. Carbon nanoparticles CNP are a prominent component of outdoor air pollution that causes pulmonary toxicity mainly through inflammation. Recently we demonstrated that mice C3H-HeJ with higher than normal pulmonary function resolved the elicited pulmonary inflammation following CNP exposure through activation of defense and homeostasis maintenance pathways. To test whether CNP-induced inflammation is affected by declined lung function, we exposed JF1-Msf JF1 mice with lower than normal pulmonary function to CNP and studied the pulmonary inflammation and its resolution.

Methods5 μg, 20 μg and 50 μg CNP Printex 90 were intratracheally instilled in JF1 mice to determine the dose response and the time course of inflammation over 7 days 20 μg dosage. Inflammation was assessed using histology, bronchoalveolar lavage BAL analysis and by a panel of 62 protein markers.

Results24 h after instillation, 20 μg and 50 μg CNP caused a 25 fold and 19 fold increased polymorphonuclear leucocytes PMN respectively while the 5 μg represented the -no observable adverse effect level- as reflected by PMN influx 9.7 × 10E3 vs 8.9 × 10E3, and BAL-lung concentrations of pro-inflammatory cytokines. Time course assessment of the inflammatory response revealed that compared to day1 the elevated BAL PMN counts 246.4 × 10E3 were significantly decreased at day 3 72.9 × 10E3 and day 7 48.5 × 10E3 but did not reach baseline levels indicating slow PMN resolution kinetics. Strikingly on day 7 the number of macrophages doubled 455.0 × 10E3 vs 204.7 × 10E3 and lymphocytes were 7-fold induced 80.6 × 10E3 vs 11.2 × 10E3 compared to day1. At day 7 elevated levels of IL1B, TNF, IL4, MDC-CCL22, FVII, and vWF were detected in JF1 lungs which can be associated to macrophage and lymphocyte activation.

ConclusionThis explorative study indicates that JF1 mice with impaired pulmonary function also exhibits delayed resolution of particle mediated lung inflammation as evident from elevated PMN and accumulation of macrophages and lymphocytes on day7. It is plausible that elevated levels of IL1B, IL4, TNF, CCL22-MDC, FVII and vWF counteract defense and homeostatic pathways thereby driving this phenomenon.

Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-12-94 contains supplementary material, which is available to authorized users.

Tobias Stoeger and Holger Schulz contributed equally to this work.

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