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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Clinical and Molecular Allergy 1/2012

Defining the molecular role of gp91phox in the immune manifestation of acute allergic asthma using a preclinical murine model

Zeitschrift:
Clinical and Molecular Allergy > Ausgabe 1/2012
Autoren:
Ena Ray Banerjee, William R Henderson Jr
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1476-7961-10-2) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

ERB conceptualized, designed and performed the experiments, evaluated the data, and wrote this manuscript. WRH provided the fund and lab space and contributed with inputs during analyses and interpretation of the results. All authors read and approved the final manuscript.

Abstract

Objective

The phenomena manifested during inflammation require interplay between circulating effector cells, local resident cells, soluble mediators and genetic host factors to establish, develop and maintain itself. Of the molecues involed in the initiation and perpetuation of acute allergic inflammation in asthma, the involvement of effector cells in redox reactions for producing O2- (superoxide anion) through the mediation of NADPH oxidase is a critical step. Prior data suggest that reactive oxygen species (ROS) produced by NADPH oxidase homologues in non-phagocytic cells play an important role in the regulation of signal transduction, while macrophages use a membrane-associated NADPH oxidase to generate an array of oxidizing intermediates which inactivate MMPs on or near them.

Materials and Methods and Treatment

To clarify the role of gp91phox subunit of NADPH oxidase in the development and progression of an acute allergic asthma phenotype, we induced allergen dependent inflammation in a gp91 phox -/- single knockout and a gp91phox-/-MMP-12-/- double knockout mouse models.

Results

In the knockout mice, both inflammation and airway hyperreactivity were more extensive than in wildtype mice post-OVA. Although OVA-specific IgE in plasma were comparable in wildtype and knockout mice, enhanced inflammatory cell recruitment from circulation and cytokine release in lung and BALf, accompanied by higher airway resistance as well as Penh in response to methacholine, indicate a regulatory role for NADPH oxidase in development of allergic asthma. While T cell mediated functions like Th2 cytokine secretion, and proliferation to OVA were upregulated synchronous with the overall robustness of the asthma phenotype, macrophage upregulation in functions such as proliferation, and mixed lymphocyte reaction indicate a regulatory role for gp91phox and an overall non-involvement or synergistic involvement of MMP12 in the response pathway (comparing data from gp91phox-/- and gp91phox-/-MMP-12-/- mice).
Zusatzmaterial
Authors’ original file for figure 1
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Literatur
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