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• W1498346321 abstract "Abstract The NADPH oxidase (NOX), an oligomeric enzyme, plays a key role in polymorphonuclear neutrophil (PMN)-mediated host defense by producing cytotoxic superoxide anion (O2). Whereas in vitro and biochemical studies have examined the assembly and activation of this important host immune defense system, few studies have examined the function of NOX in human patients with primary immunodeficiency other than chronic granulomatous disease. We studied the activation of NOX in PMN from patients with two distinct immunodeficiencies, IL-1R-associated kinase (IRAK)4 deficiency and NF-κB essential modulator (NEMO or IκB kinase γ) deficiency. We observed impaired O2 generation by LPS-treated and fMLP-activated IRAK4-deficient PMN that correlated with decreased phosphorylation of p47phox and subnormal translocation of p47phox, p67phox, Rac2, and gp91phox/Nox2 to the membranes indicating that TLR4 signaling to the NOX activation pathway requires IRAK4. NEMO-deficient PMN generated significantly less O2 in response to LPS-primed fMLP and translocated less p67phox than normal PMN, although p47phox and Rac2 translocation were normal. Generally, responses of NEMO-deficient cells were intermediate between IRAK4-deficient cells and normal cells. Decreased LPS- and fMLP-induced phosphorylation of p38 MAPK in both IRAK4- and NEMO-deficient PMN implicates additional signal transduction pathways in regulating PMN activation by LPS and fMLP. Decreased activation of NOX may contribute to the increased risk of infection seen in patients with IRAK4 and NEMO deficiency." @default.
• W1498346321 created "2016-06-24" @default.
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• W1498346321 date "2009-05-15" @default.
• W1498346321 modified "2023-10-05" @default.
• W1498346321 title "Impaired Priming and Activation of the Neutrophil NADPH Oxidase in Patients with IRAK4 or NEMO Deficiency" @default.
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• W1498346321 doi "https://doi.org/10.4049/jimmunol.0802512" @default.
• W1498346321 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3733113" @default.
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• W1498346321 hasPublicationYear "2009" @default.
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