Role of Oxidative Stress in Ultrafine Particle-Induced Exacerbation of Allergic Lung Inflammation.

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Am J Respir Crit Care Med. 2009 Mar 5. [Epub ahead of print] Links

Role of Oxidative Stress in Ultrafine Particle-Induced Exacerbation of

Allergic Lung Inflammation.

http://www.ncbi.nlm.nih.gov/pubmed/19264975?ordinalpos=3 & itool=Email.EmailReport\

..Pubmed_ReportSelector.Pubmed_RVDocSum Alessandrini F, Beck-Speier I,

Krappmann D, Weichenmeier I, Takenaka S, Karg E, Kloo B, Schulz H, Jakob

T, Mempel M, Behrendt H.

Division of Environmental Dermatology and Allergy , Helmholtz

Zentrum/Technische Universitat Munchen, ZAUM Center for Allergy and

Environment, Neuherberg and Munich, Germany; Focus Network Nanoparticles and

Health (NanoHealth) , Helmholtz Zentrum Munchen, German Research Center for

Environmental Health (GmbH), Neuherberg, Germany.

RATIONALE: The effects of ultrafine particles inhalation on allergic airway

inflammation is of growing interest. The mechanisms underlying these effects

are currently under investigation. OBJECTIVES: To investigate the role of

oxidative stress on the adjuvant activity of inhaled elemental carbon ultrafine

particles (EC-UFP) on allergic airway inflammation. METHODS:

Ovalbumin-sensitized mice were exposed to EC-UFP(504microHg/m(3) for 24 h) or

filtered air immediately prior to allergen challenge and systemically treated

with Nacetylcysteine or vehicle prior and during EC-UFP inhalation. Allergic

inflammation was measured up to one week after allergen challenge by means of

bronchoalveolar lavage, cytokine/total protein assays, lung function and

histology. Isoprostane levels in lung tissue served to measure oxidative stress.

Transmission electron microscopy served to localize ECUFP in lung tissue and

both EMSA and immunohistochemistry to quantify/localize NF-kappaB

activation. MAIN RESULTS: In sensitized and challenged mice EC-UFP inhalation

increased allergen-induced lung lipid peroxidation and NF-kappaB activation in

addition to inflammatory infiltrate, cytokine release and airway

hyperresponsiveness. Prominent NF-kappaB activation was observed in the same

cell types in which EC-UFP were detected. N-acetylcysteine treatment

significantly reduced the adjuvant activity of EC-UFP. In non sensitized or

sensitized but not challenged mice EC-UFP exposure induced a moderate increase

in isoprostanes, but no significant effect on other parameters of lung

inflammation. CONCLUSIONS: Our findings demonstrate a critical role for

oxidative stress in EC-UFP-induced augmentation of allergen-induced lung

inflammation, where EC-UFP exposure has potentiating effects in lung allergic

inflammation. Our data support the concept that allergic individuals are more

susceptible to the adverse health effects of EC-UFP.

PMID: 19264975 [PubMed - as supplied by publisher]