High vascular endothelial growth factor levels in NZW mice do not correlate with collagen deposition in allergic asthma.
BACKGROUND
Eosinophils contribute to the early features of allergic lung inflammation through the generation and release of a plethora of mediators. Eosinophil peroxidase (EPO) is one of the eosinophil granule proteins involved in the early response, but its participation in airway remodeling is not established. The present study addressed this question comparing an EPO-deficient mouse strain (NZW) with BALB/c and C57Bl/c strains.


METHODS
Mice were immunized with ovalbumin/alum, challenged twice with ovalbumin aerosol, and lung responses were measured at day 22 or 28. Collagen, mucus and eosinophils were determined in lung sections stained with picrosirius, periodic acid-Schiff or hematoxylin-eosin; transforming growth factor-beta and vascular endothelial growth factor were determined by ELISA, lipid bodies by enumeration in osmium-stained eosinophils, and airway reactivity to methacholine in isolated lung preparations.


RESULTS
NZW mice showed significantly less collagen around bronchi and blood vessels, less mucus and less eosinophils around bronchi. Eosinophil lipid body formation and airway hyperreactivity were comparable among strains. Levels of transforming growth factor-beta were also comparable; however, the NZW mice showed much higher levels of vascular endothelial growth factor, even under basal conditions.


CONCLUSIONS
In allergic lung inflammation, the combination of EPO deficiency and overexpression of VEGF found in NZW mice is associated with less collagen deposition, less mucus and reduced tissue eosinophilia. Eosinophil activation and airway hyperreactivity in NZW mice were similar to the other strains.
Vasquez-Pinto
Luciana M C
LM
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Landgraf
Richardt G
RG
Bozza
Patrícia T
PT
Jancar
Sonia
S
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003094:Collagen / Q000276:immunology*; D047209:Eosinophil Peroxidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004802:Eosinophilia; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D016212:Transforming Growth Factor beta / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D016210:Methacholine Chloride; D010047:Ovalbumin; D003094:Collagen; D047209:Eosinophil Peroxidase