Extensive eosinophil degranulation and peroxidase-mediated oxidation of airway proteins do not occur in a mouse ovalbumin-challenge model of pulmonary inflammation.
Paradigms of eosinophil effector function in the lungs of asthma patients invariably depend on activities mediated by cationic proteins released from secondary granules during a process collectively referred to as degranulation. In this study, we generated knockout mice deficient for eosinophil peroxidase (EPO) to assess the role(s) of this abundant secondary granule protein in an OVA-challenge model. The loss of EPO had no effect on the development of OVA-induced pathologies in the mouse. The absence of phenotypic consequences in these knockout animals extended beyond pulmonary histopathologies and airway changes, as EPO-deficient animals also displayed OVA-induced airway hyperresponsiveness after provocation with methacholine. In addition, EPO-mediated oxidative damage of proteins (e.g., bromination of tyrosine residues) recovered in bronchoalveolar lavage from OVA-treated wild-type mice was <10% of the levels observed in bronchoalveolar lavage recovered from asthma patients. These data demonstrate that EPO activities are inconsequential to the development of allergic pulmonary pathologies in the mouse and suggest that degranulation of eosinophils recruited to the lung in this model does not occur at levels comparable to those observed in humans with asthma.
Denzler
K L
KL
Department of Biochemistry and Molecular Biology, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA.
Borchers
M T
MT
Crosby
J R
JR
Cieslewicz
G
G
Hines
E M
EM
Justice
J P
JP
Cormier
S A
SA
Lindenberger
K A
KA
Song
W
W
Wu
W
W
Hazen
S L
SL
Gleich
G J
GJ
Lee
J J
JJ
Lee
N A
NA
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015550:Cell Degranulation / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D007274:Injections, Intraperitoneal; D008168:Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D017384:Sequence Deletion
D000485:Allergens; D011506:Proteins; D010047:Ovalbumin; D047209:Eosinophil Peroxidase; D010544:Peroxidases