Iron-mediated dismutation of superoxide anion augments antigen-induced allergic inflammation: effect of lactoferrin.
BACKGROUND
The authors previously showed that pollen grain-, pollen grain extract-. and subpollen particle-induced allergic inflammation in lungs and eyes is robustly augmented by their intrinsic NAD(P)H oxidase activity. Here they sought to determine whether lactoferrin (LF), an iron-binding protein and immune modulator, decreases allergic inflammation induced by ragweed (Ambrosia artemisiifolia) pollen grain extract (RWE).


METHODS
The impact of LF on NAD(P)H oxidase in pollen grains and reactive oxygen species (ROS) levels in vitro and in the lungs of experimental animals was assessed by use of redox-sensitive probes and specific inhibitors. The influence of LF on RWE-induced allergic inflammation was determined in a mouse experimental model of asthma.


RESULTS
The data show that the intrinsic NAD(P)H oxidase of pollen grains generates superoxide anion (O2-) and that LF does not alter its enzymatic activity, as shown by nitroblue tetrazolium and cytochrome c assays. On the other hand, LF significantly decreased H(2)- O(2)- and lipid peroxide (4-hydroxynoneal and malondialdehyde) levels in airway lining fluids and lung epithelium after intranasal challenge of naive or sensitized mice with RWE. Furthermore, a single dose of LF prevented/decreased the abundance of the RWE-induced robust accumulation of inflammatory and mucin-producing cells in airways and subepithelial compartments and decreased airway hyperreactivity.


CONCLUSIONS
These data suggest that the reduced conversion of NAD(P)H oxidase-generated O(2)- into H(2)- O(2)- and/or OH, which in turn synergistically enhanced pollen antigen-induced airway inflammation, is due to the iron-binding capacity of LF. These results support the utility of LF in human allergic inflammatory disorders.
Chodaczek
Grzegorz
G
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Saavedra-Molina
Alfredo
A
Bacsi
Attila
A
Kruzel
Marian L
ML
Sur
Sanjiv
S
Boldogh
Istvan
I
D000485:Allergens / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D052179:Antigens, Plant; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007781:Lactoferrin / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D010940:Plant Proteins / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism*
D000485:Allergens; C026967:Amb a I protein, Ambrosia artemisiifolia; D052179:Antigens, Plant; D010940:Plant Proteins; D013481:Superoxides; D007781:Lactoferrin