Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthma.
Pollen grains contain reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and in contact with mucosal surfaces generate superoxide anion (O2*-). In the presence of iron, O2*- may be converted to more reactive oxygen radicals, such as to H2O2 and/or *OH, which may augment antigen-induced airway inflammation. The aim of the study was to examine the impact of lactoferrin (LF), an iron-binding protein, on ragweed (Ambrosia artemisiifolia) pollen extract (RWE)-induced cellular oxidative stress levels in cultured bronchial epithelial cells and accumulation of inflammatory and mucin-producing cells in airways in a mouse model of allergic airway inflammation. Results show that LF lowered RWE-induced increase in cellular reactive oxygen species (ROS) levels in bronchial epithelial cells. Most importantly, LF significantly decreased accumulation of eosinophils into airways and subepithelium of intranasally challenged, sensitized mice. LF also prevented development of mucin-producing cells. Amb a 1, the major allergenic ragweed pollen antigen lacking NADPH oxidase activity, induced low-grade airway inflammation. When administered along with glucose oxidase (G-ox), a superoxide-generating enzyme, Amb a 1 induced robust airway inflammation, which was significantly lowered by LF. Surprisingly, LF decreased also inflammation caused by Amb a 1 alone. Iron-saturated hololactoferrin had only a marginal effect on RWE-induced cellular ROS levels and RWE- or Amb a 1 plus G-ox-induced inflammation. We postulate that free iron in the airways chemically reduces O2*- to more reactive species which augment antigen-induced inflammation in a mouse model of asthma. Our results suggest the utility of LF in human allergic inflammatory disorders.
Kruzel
Marian L
ML
PharmaReview Corporation, Inc., Houston, TX, USA. mkruzel@ev1.net
Bacsi
Attila
A
Choudhury
Barun
B
Sur
Sanjiv
S
Boldogh
Istvan
I
D000485:Allergens / Q000276:immunology*; D031164:Ambrosia / Q000276:immunology; 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 / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D010940:Plant Proteins / Q000276:immunology; D011058:Pollen / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000485:Allergens; C026967:Amb a I protein, Ambrosia artemisiifolia; D052179:Antigens, Plant; D010940:Plant Proteins; D017382:Reactive Oxygen Species; D007781:Lactoferrin