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Title: | Endogenous myeloperoxidase promotes neutrophil-mediated renal injury, but attenuates T cell immunity inducing crescentic glomerulonephritis. | Authors: | Holdsworth S.R. ;Kitching A.R. ;Odobasic D.;Semple T.J. | Institution: | (Odobasic, Kitching, Semple, Holdsworth) Centre for Inflammatory Diseases, Monash University, Department of Medicine, Clayton, Vic., Australia (Holdsworth) Department of Medicine, Monash University, Monash Medical Centre, 246 Clayton Road, Clayton, Vic. 3168, Australia | Issue Date: | 16-Oct-2012 | Copyright year: | 2007 | Publisher: | American Society of Nephrology (1725 I Street NW, Suite 510, Washington DC 20006, United States) | Place of publication: | United States | Publication information: | Journal of the American Society of Nephrology. 18 (3) (pp 760-770), 2007. Date of Publication: March 2007. | Abstract: | Myeloperoxidase (MPO) is an enzyme that is found in neutrophils and monocytes/macrophages. Intracellularly, it plays a major role in microbial killing, but extracellularly, it may cause host tissue damage. The role of endogenous MPO was studied during neuhophil-mediated (heterologous) and T helper 1 (Th1)/macrophage-mediated (autologous) phases of crescentic glomerulonephritis. Glomerulonephritis was induced in C57BL/6 wild-type (WT) and MPO-deficient (MPO-/-) mice by intravenous injection of sheep anti-mouse glomerular basement membrane globulin. MPO activity was increased in kidneys of WT mice during both the heterologous and autologous phases of glomerulonephritis. During the heterologous phase of glomerulonephritis, proteinuria was decreased, whereas glomerular neutrophil accumulation and F-selectin expression were enhanced in MPO-/- mice. In the autologous, crescentic phase of glomerulonephritis, MPO-/- mice had increased accumulation of CD4+ cells and macrophages in glomeruli compared with WT mice. However, no difference in renal injury (crescent formation, proteinuria, and serum creatinine levels) was observed. Neutrophils and macrophages from MPO-/- mice exhibited reduced production of reactive oxygen species. Assessment of systemic immunity to sheep globulin showed that MPO-/- mice had increased splenic CD4+ cell proliferation, cytokine production, and dermal delayed-type hypersensitivity, as well as enhanced levels of circulating IgG, IgG1, and IgG3. MPO-/- mice also had an augmented Th1:Th2 ratio compared with WT mice (IFN-gamma:IL-4 and IgG3:IgG1 ratios). These results suggest that endogenous MPO locally contributes to glomerular damage during neutrophil-mediated glomerulonephritis, whereas it attenuates initiation of the adaptive immune response inducing crescentic, autologous-phase glomerulonephritis by suppressing T cell proliferation, cytokine production, and Th1:Th2 ratio. Copyright © 2007 by the American Society of Nephrology. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1681/ASN.2006040375 | PubMed URL: | 17267745 [http://www.ncbi.nlm.nih.gov/pubmed/?term=17267745] | ISSN: | 1046-6673 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/31795 | Type: | Article | Subjects: | lymphocyte proliferation macrophage male monocyte mouse *neutrophil nonhuman priority journal protein expression proteinuria *rapidly progressive glomerulonephritis/et [Etiology] sheep spleen cell *T lymphocyte Th1 cell Th2 cell tissue injury/et [Etiology] wild type CD4 antigen/ec [Endogenous Compound] creatinine/ec [Endogenous Compound] gamma interferon/ec [Endogenous Compound] globulin immunoglobulin antibody immunoglobulin G/ec [Endogenous Compound] immunoglobulin G1/ec [Endogenous Compound] immunoglobulin G3/ec [Endogenous Compound] interleukin 4/ec [Endogenous Compound] *myeloperoxidase/ec [Endogenous Compound] PADGEM protein/ec [Endogenous Compound] reactive oxygen metabolite/ec [Endogenous Compound] immune response adaptive immunity animal cell animal experiment animal model animal tissue article CD4 lymphocyte count cell proliferation *cellular immunity controlled study creatinine blood level cytokine production delayed hypersensitivity enzyme activity glomerulus basement membrane *kidney injury/et [Etiology] enzyme activity glomerulus basement membrane immune response *kidney injury / *etiology lymphocyte proliferation macrophage male monocyte mouse *neutrophil nonhuman priority journal protein expression proteinuria *rapidly progressive glomerulonephritis / *etiology sheep spleen cell *T lymphocyte Th1 cell Th2 cell tissue injury / etiology animal tissue animal model animal experiment animal cell adaptive immunity wild type article CD4 lymphocyte count cell proliferation *cellular immunity controlled study creatinine blood level cytokine production delayed hypersensitivity |
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