Eosinophil Peroxidase Deficiency in New Zealand White Mice

Ohmori, Jun; Tokunaga, Hiroko; Ezaki, Taichi; Maruyama, Hidenori; Nawa, Yukifumi

doi:10.1159/000237341

Cited by 9 publications

(9 citation statements)

References 11 publications

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“…However, notable clinical symptoms were absent in these cases, as the identification of EPO-deficient patients occurred randomly during studies unrelated to asthma or allergic disease (33). A similar EPO deficiency was also described in a unique substrain of New Zealand White (NZW) mice (34). This deficiency in NZW mice led to comparable effects (i.e., relative to human EPO-deficient patients) on the electron microscopic ultrastructure of eosinophil secondary granules.…”

mentioning

confidence: 57%

Extensive Eosinophil Degranulation and Peroxidase-Mediated Oxidation of Airway Proteins Do Not Occur in a Mouse Ovalbumin-Challenge Model of Pulmonary Inflammation

Denzler

Borchers

Crosby

et al. 2001

The Journal of Immunology

114

102

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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.

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mentioning

confidence: 57%

Extensive Eosinophil Degranulation and Peroxidase-Mediated Oxidation of Airway Proteins Do Not Occur in a Mouse Ovalbumin-Challenge Model of Pulmonary Inflammation

Denzler

Borchers

Crosby

et al. 2001

The Journal of Immunology

114

102

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“…They contribute to the early features of allergic inflammation through the generation of lipid mediators and release of granule contents [1]. Eosinophils store cationic and cytotoxic proteins in their secondary granules, among them the eosinophil peroxidase (EPO), a cationic heme-containing protein that corresponds to nearly 25% of the total protein mass in eosinophil secondary granules [10]. EPO was shown to be cytotoxic to the epithelial cells of the bronchi [11], and in consequence, the airway smooth muscle becomes more reactive to various stimuli.…”

Section: Introductionmentioning

confidence: 99%

“…The present study investigated the contribution of EPO to some aspects of the remodeling process in experimental asthma. To this purpose, we induced an allergic lung inflammation in a mouse strain (NZW) which exhibits EPO deficiency due to a spontaneous mutation [10] and measured collagen deposition around the bronchi and vessels, mucus formation, airway VEGF and TGF-β levels and airway hyperreactivity. We also examined eosinophil numbers in bronchoalveolar lavage and around bronchi, as well as their lipid body formation, indicative of activation.…”

Section: Introductionmentioning

confidence: 99%

High Vascular Endothelial Growth Factor Levels in NZW Mice Do Not Correlate with Collagen Deposition in Allergic Asthma

Vasquez-Pinto

Landgraf²,

Bozza³

et al. 2006

Int Arch Allergy Immunol

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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-β 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-β 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.

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“…NZW mice themselves are normally clinically healthy, but they still present subclinical features of SLE such as nephritis, increased susceptibility to environmental insults 10 and to immune‐mediated end‐organ damage 13 . In addition, these animals have been shown to present a deficiency in eosinophil peroxidase (EPO), 14,15 abnormal inflammatory responses to intraperitoneal insult, 16 and altered levels of pro‐angiogenic and pro‐fibrogenic factors 15,17 …”

mentioning

confidence: 99%

Mechanisms of wound healing responses in lupus‐prone New Zealand White mouse strain

Campos

Bakhle

Andrade

2008

Wound Repair Regeneration

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Host responses to synthetic implants are analogous to healing, the process of repair that follows injury. Normally, the processes of wound healing follow well-established patterns but conditions such as autoimmune diseases profoundly affect tissue repair. We have analyzed sponge-induced wound healing responses in lupus-prone New Zealand White and control (Balb/c) mouse strains by measuring inflammation, extracellular matrix deposition, angiogenesis, and cytokine production in polyether-polyurethane sponge implanted subcutaneously in male mice of these two strains. Although there was no difference in the gross appearance of the implants, further analysis of the wound healing responses, induced from 7 to 21 days post implantation, disclosed important differences between the New Zealand White and Balb/c strains. The intensity of inflammation (circulating tumor necrosis factor-alpha and inflammatory leukocytes levels) was lower but implant fibrosis (collagen and transforming growth factor-beta1) was higher in New Zealand White, compared with Balb/c mice. Angiogenesis (hemoglobin, vascular endothelial growth factor, and vascularity) in New Zealand White implants peaked earlier than in Balb/c mice. In conclusion, we have shown that wound healing responses are clearly different in this strain of lupus-prone mice and suggest that this pattern of repair was critically influenced by impaired inflammation and accelerated angiogenesis in the New Zealand White strain.

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Eosinophil Peroxidase Deficiency in New Zealand White Mice

Cited by 9 publications

References 11 publications

Extensive Eosinophil Degranulation and Peroxidase-Mediated Oxidation of Airway Proteins Do Not Occur in a Mouse Ovalbumin-Challenge Model of Pulmonary Inflammation

Extensive Eosinophil Degranulation and Peroxidase-Mediated Oxidation of Airway Proteins Do Not Occur in a Mouse Ovalbumin-Challenge Model of Pulmonary Inflammation

High Vascular Endothelial Growth Factor Levels in NZW Mice Do Not Correlate with Collagen Deposition in Allergic Asthma

Mechanisms of wound healing responses in lupus‐prone New Zealand White mouse strain

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