ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation.
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).
Boldogh
Istvan
I
Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, Texas 77555, USA.
Bacsi
Attila
A
Choudhury
Barun K
BK
Dharajiya
Nilesh
N
Alam
Rafeul
R
Hazra
Tapas K
TK
Mitra
Sankar
S
Goldblum
Randall M
RM
Sur
Sanjiv
S
D000447:Aldehydes / Q000378:metabolism; D000485:Allergens / Q000378:metabolism*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004848:Epithelium / Q000201:enzymology / Q000473:pathology; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D019255:NADPH Oxidases / Q000378:metabolism*; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000201:enzymology / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011058:Pollen / Q000201:enzymology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000201:enzymology* / Q000473:pathology
D000447:Aldehydes; D000485:Allergens; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; C027576:4-hydroxy-2-nonenal; D019803:Glutathione Disulfide