Female X-Chromosome Mosaicism for NOX2 Deficiency Presents Unique Inflammatory Phenotype and Improves Outcome in Polymicrobial Sepsis
| Autor: | Stephanie Federici, Pal Pacher, Rachna Chandra, Zoltan H. Nemeth, Zoltán Spolarics, Edwin A. Deitch, György Haskó, Béla Horváth |
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| Rok vydání: | 2011 |
| Předmět: |
Male
X Chromosome Phagocyte Neutrophils medicine.medical_treatment Immunology Bacteremia Bone Marrow Cells Inflammation Punctures Biology Article Sepsis Leukocyte Count Mice medicine Animals Immunology and Allergy Cecum Ligation Mice Knockout CD11b Antigen Membrane Glycoproteins NADPH oxidase Mosaicism NADPH Oxidases Flow Cytometry medicine.disease Bacterial Load Pathophysiology Respiratory burst Mice Inbred C57BL medicine.anatomical_structure Cytokine NADPH Oxidase 2 biology.protein Cytokines Female Bone marrow medicine.symptom |
| Zdroj: | The Journal of Immunology. 186:6465-6473 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1100205 |
| Popis: | Cellular X-chromosome mosaicism, which is unique to females, may be advantageous during pathophysiological challenges compared with the single X-chromosome machinery of males, and it may contribute to gender dimorphism in the inflammatory response. We tested the hypothesis of whether cellular mosaicism for the X-linked gp91phox (NOX2) deficiency, the catalytic component of the superoxide anion-generating NADPH oxidase complex, is advantageous during polymicrobial sepsis. Deficient, wild-type (WT), and heterozygous/mosaic mice were compared following polymicrobial sepsis initiated by cecal ligation and puncture. Compared with WT littermates, sepsis-induced mortality was improved in deficient mice, as well as in mosaic animals carrying both deficient and WT phagocyte subpopulations. In contrast, blood bacterial counts were greatest in deficient mice. Consistent with poor survival, WT mice also showed the most severe organ damage following sepsis. In mosaic animals, the deficient neutrophil subpopulations displayed increased organ recruitment and elevated CD11b membrane expression compared with WT neutrophil subpopulations within the same animal. The dynamics of sepsis-induced blood and organ cytokine content and WBC composition changes, including lymphocyte subsets in blood and bone marrow, showed differences among WT, deficient, and mosaic subjects, indicating that mosaic mice are not simply the average of the deficient and WT responses. Upon oxidative burst, interchange of oxidants between WT and deficient neutrophil subpopulations occurred in mosaic mice. This study suggests that mice mosaic for gp91phox expression have multiple advantages compared with WT and deficient mice during the septic course. |
| Databáze: | OpenAIRE |
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