The online version of this article (doi:10.1186/1476-7961-10-2) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
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.
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.
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.
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).
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De Ravin SS, Zarember KA, Long-Priel D, Chan KC, Fox SD, Gallin JI, Kuhns DB, Malech HL: Tryptophan/kynurenine metabolism in human leukocytes is independent of superoxide and is fully maintained in chronic granulomatous disease. Blood. 2010, 116 (10): 1755-60. 10.1182/blood-2009-07-233734 PubMedCentralCrossRefPubMed
Leverence JT, Medhora M, Konduri GG, Sampath V: Lipopolysaccharide-induced cytokine expression in alveolar epithelial cells: Role of PKCζ-mediated p47phox phosphorylation. Chem Biol Interact 2010.
Santilli G, Almarza E, Brendel C, Choi U, Beilin C, Blundell MP, Haria S, Parsley KL, Kinnon C, Malech HL, Bueren JA, Grez M, Thrasher AJ: Biochemical Correction of X-CGD by a Novel Chimeric Promoter Regulating High Levels of Transgene Expression in Myeloid Cells. Mol Ther 2010.
Yu L, Cross AR, Zhen L, Dinauer MC: Functional Analysis of NADPH Oxidase in Granulocytic Cells Expressing a D488-497 gp91 phox Deletion Mutant. Blood. 1999, 94: 2497-2504. PubMed
Kobayashi SD: Neutrophils in the innate immune response. Arch Immunol Ther Exp. 2005, 53: 505-517.
Ena Ray Banerjee: Triple selectin knockout (ELP-/-) mice fail to develop OVA-induced acute asthma phenotype. Journal of Inflammation. 2011, 8: 19. 10.1186/1476-9255-8-19 CrossRef
Ena Ray Banerjee, Henderson WR Jr: NADPH oxidase has a regulatory role in acute allergic asthma. Journal of Advanced Laboratory Research in Biology. 2011, 2 (3): 103-120. (ISSN 0976-7614).
Ena Ray Banerjee, Jiang Y, Henderson WR Jr, Latchman YL, Papayannopoulou T: Absence of α4 but not β2 integrins restrains the development of chronic allergic asthma using mouse genetic models. Exp Hematol. 2009, 37: 715-727. 10.1016/j.exphem.2009.03.010 CrossRef
Ena Ray Banerjee, Latchman YL, Jiang Y, Priestley GV, Papayannopoulou T: Distinct changes in adult lymphopoiesis in Rag2-/- mice fully reconstituted by α4-deficinet adult bone marrow cells. Exp Hematol. 2008, 36 (8): 1004-13. 10.1016/j.exphem.2008.03.008 CrossRef
Ulyanova T, Ena Ray Banerjee, Priestley GV, Scott LM, Papayannopoulou T: Unique and redundant roles of alpha4 and beta2 integrins in kinetics of recruitment of lymphoid vs myeloid cell subsets to the inflamed peritoneum revealed by studies of genetically deficient mice. Exp hematol. 2007, 35 (8): 1256-65. 10.1016/j.exphem.2007.04.015 PubMedCentralCrossRefPubMed
Ena Ray Banerjee, Jiang Y, Henderson WR Jr, Scott LM, Papayannopoulou T: Alpha4 and beta2 integrins have non-overlapping roles in asthma development, but for optimal allergen sensitization only alpha4 is critical. Exp Hematol. 2007, 35 (4): 605-17. 10.1016/j.exphem.2007.01.052 CrossRef
Nijmeh J, Moldobaeva A, Wagner EM: Role of ROS in ischemia-induced lung angiogenesis. Am J Pathol - Lung physiol. 2010, 299 (4): L539-L541.
Murillo I, d Henderson LM: Expression of gp91 phox /Nox2 in COS-7 cells: cellular localization of the protein and the detection of outward proton currents. Biochem J. 2005, 385 (649-657):
Williams M, Shatyanski K, chen H: The phagocyte NADPH oxidase (NOX2) regulates adaptive immune response at the level of both T cells and APCs. J Immunol. 2010, 184 (Meeting Abstract Supplement): 138.7.
- Defining the molecular role of gp91phox in the immune manifestation of acute allergic asthma using a preclinical murine model
Ena Ray Banerjee
William R Henderson Jr
- BioMed Central
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