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Two Cytosolic Neutrophil Oxidase Components Absent in Autosomal Chronic Granulomatous Disease
Abstract
Neutrophils kill microorganisms with oxygen radicals generated by an oxidase that uses the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) as substrate. This system requires both membrane and cytosolic components and is defective in patients with chronic granulomatous disease. A cytosolic complex capable of activating latent membrane oxidase was eluted from guanosine triphosphate-agarose and was used to raise polyclonal antiserum that recognized 47- and 67-kilodalton proteins. These proteins were restricted to the cytosol of myeloid cells. Both proteins were associated with NADPH oxidase-activating capacity when neutrophil cytosol was purified on nucleotide affinity matrices or molecular sizing columns. Neutrophils from patients with two different forms of autosomal chronic granulomatous disease lacked either the 47- or 67-kilodalton protein.
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“For example, H2O2 can also modulate genes expression by epigenetic modification and activate transcription factors such as AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κβ, NOTCH, SP1, SCREB-1 and FOXO family [14,15,16,17,18,19,20,21,22].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [19]
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Interactions between the components of the human nadph oxidase: intrigues in the phox family
Leusen, J. H. W., Verhoeven, A. J., & Roos, D. (1996) · Journal of Laboratory and Clinical Medicine · doi:10.1016/s0022-2143(96)90043-8 · Cited by 117
Metadata
- Authors
- Volpp, B. D., Nauseef, W. M., & Clark, R. A.
- Affiliations
- University of Iowa (US)
- Venue
- Science
- Published
- 1988-12-02
- Volume
- 242
- Issue
- 4883
- Pages
- 1295-1297
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2014594279
- Cited by
- 407
- References
- 49
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 11 · 2018: 3 · 2017: 2 · 2016: 8 · 2015: 1 · 2014: 9 · 2013: 11 · 2012: 2
- FWCI
- 13.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX000513)
- U.S. Public Health Service (DM 01295)
- National Institute of Allergy and Infectious Diseases (AI 20866, R01AI020866)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- chronic granulomatous disease, neutrophil NADPH oxidase, NADPH oxidase activation, oxygen free radicals, myeloid cells
- MeSH terms
- Cytosol, Granulomatous Disease, Chronic, Humans, Molecular Weight, NADH, NADPH Oxidoreductases, Neutrophils, Superoxides, Blotting, Western, GTP-Binding Proteins, NADPH Oxidases
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