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ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation
Istvan Boldogh, … , Randall M. Goldblum, Sanjiv Sur
Istvan Boldogh, … , Randall M. Goldblum, Sanjiv Sur
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2169-2179. https://doi.org/10.1172/JCI24422.
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Research Article Immunology

ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation

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Abstract

Pollen exposure induces allergic airway inflammation in sensitized subjects. The role of antigenic pollen proteins in the induction of allergic airway inflammation is well characterized, but the contribution of other constituents in pollen grains to this process is unknown. Here we show that pollen grains and their extracts contain intrinsic NADPH oxidases. The pollen NADPH oxidases rapidly increased the levels of ROS in lung epithelium as well as the amount of oxidized glutathione (GSSG) and 4-hydroxynonenal (4-HNE) in airway-lining fluid. These oxidases, as well as products of oxidative stress (such as GSSG and 4-HNE) generated by these enzymes, induced neutrophil recruitment to the airways independent of the adaptive immune response. Removal of pollen NADPH oxidase activity from the challenge material reduced antigen-induced allergic airway inflammation, the number of mucin-containing cells in airway epithelium, and antigen-specific IgE levels in sensitized mice. Furthermore, challenge with Amb a 1, the major antigen in ragweed pollen extract that does not possess NADPH oxidase activity, induced low-grade allergic airway inflammation. Addition of GSSG or 4-HNE to Amb a 1 challenge material boosted allergic airway inflammation. We propose that oxidative stress generated by pollen NADPH oxidases (signal 1) augments allergic airway inflammation induced by pollen antigen (signal 2).

Authors

Istvan Boldogh, Attila Bacsi, Barun K. Choudhury, Nilesh Dharajiya, Rafeul Alam, Tapas K. Hazra, Sankar Mitra, Randall M. Goldblum, Sanjiv Sur

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Figure 1

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Pollen grain extracts show NADPH oxidase activity. (A) Reduction of NBT ...
Pollen grain extracts show NADPH oxidase activity. (A) Reduction of NBT to formazan by allergenic extracts using NBT assay in the presence (+) or absence (–) of NADPH. RWE, RWEH, and Amb a 1 were tested. X+XO were used as a positive control. #P < 0.001; ##P < 0.0001. (B) pRWEOX+-induced NBT reduction is inhibited by NADPH oxidase inhibitors DPI, QA, and SOD. The presence or absence of NADPH in the reaction mixture is indicated. (C) NBT reduction by allergenic extracts in situ after nondenaturing PAGE. RWEH, heat-inactivated oak extract (OakH), and heat-inactivated timothy grass extract (TimothyH) are shown. (D) Detection of p67phox by Western blot analysis using a rabbit anti-human p67phox antibody. (E and F) Immunolocalization of p67phox in ragweed pollens detected by fluorescence microscopy using anti-p67phox antibody (E) or normal rabbit IgG control (F). Right panels show differential interference contrast images of the same pollens. Magnification, ×600. (G) Kinetics of O2•– generation determined by cytochrome c assay. Shown are cytochrome c (filled diamonds); cytochrome c plus pRWEOX+ (filled squares); cytochrome c plus NADPH (open triangles); cytochrome c plus pRWEOX+ and NADPH (open squares); and cytochrome c plus pRWEOX+, NADPH, and SOD (filled triangles).

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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