Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 115, Issue 8, Pages 2169-2179Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI24422
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Funding
- NCI NIH HHS [R01 CA084461, CA84461] Funding Source: Medline
- NHLBI NIH HHS [N01HV28184, 1R01HL071163-01A2, R01 HL071163] Funding Source: Medline
- NIAID NIH HHS [P01 AI46004, P01 AI062885] Funding Source: Medline
- NIEHS NIH HHS [ES06676, P30 ES006676] Funding Source: Medline
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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 I 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).
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