{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T19:22:26Z","timestamp":1778613746328,"version":"3.51.4"},"reference-count":51,"publisher":"BMJ","issue":"8","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Gut"],"accepted":{"date-parts":[[2017,5,1]]},"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Cirrhosis downregulates phagocyte oxidant production via their antibacterial superoxide-generating system, NADPH oxidase (NOX2) and increases patients\u2019 susceptibility to infection and mortality rate. To explore novel biochemical parameters that explain susceptibility to infections, we investigated the expression of NOX2 and partners in neutrophils of patients with severe alcoholic cirrhosis and have provided a novel approach to restore superoxide production capacity in patients\u2019 neutrophils and blood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Neutrophils were isolated from patients with decompensated alcoholic cirrhosis. NOX2 activity was assessed after stimulation of purified neutrophils or whole blood with the bacterial-derived peptide fMet-Leu-Phe. The expression of NOX2 and partners was studied by western blot analysis, flow cytometry and reverse transcription-PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The impaired superoxide production by patients\u2019 neutrophils was associated with a severe deficient expression of the NADPH oxidase catalytic core flavocytochrome-b558 (gp91\n                      <jats:italic>\n                        <jats:sup>phox<\/jats:sup>\n                      <\/jats:italic>\n                      \/NOX2 and p22\n                      <jats:italic>\n                        <jats:sup>phox<\/jats:sup>\n                      <\/jats:italic>\n                      ), its cytosolic partner p47\n                      <jats:italic>\n                        <jats:sup>phox<\/jats:sup>\n                      <\/jats:italic>\n                      but not p67\n                      <jats:italic>\n                        <jats:sup>phox<\/jats:sup>\n                      <\/jats:italic>\n                      . NOX2 expression decreased rapidly by protein degradation involving elastase released during degranulation of healthy neutrophils stimulated with fMet-Leu-Phe, or highly present in patients\u2019 plasma. Interestingly, the deficient superoxide production was reversed by treatment of patients\u2019 neutrophils and whole blood with toll-like receptor 7\/8 (TLR7\/8) agonists. This treatment stimulated a rapid NOX2 transcription and translation through a process involving mammalian target of rapamycin (mTOR) whose expression was also deficient in patients\u2019 neutrophils. NOX2 expression was also increased by the TLR4 agonist lipopolysaccharide but with only a modest improvement of reactive oxygen species production.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Impairment of neutrophil oxidants production in alcoholic cirrhosis is associated with NOX2 degradation and deficient mTOR-dependent translational machinery. The NOX2 depletion can be reversed via TRL7\/8 activation and might be used to restore antimicrobial responses of immunocompromised patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2016-313443","type":"journal-article","created":{"date-parts":[[2017,6,10]],"date-time":"2017-06-10T20:20:16Z","timestamp":1497126016000},"page":"1505-1516","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["NADPH oxidase depletion in neutrophils from patients with cirrhosis and restoration via toll-like receptor 7\/8 activation"],"prefix":"10.1136","volume":"67","author":[{"given":"Lo\u00efc","family":"Rolas","sequence":"first","affiliation":[{"name":"INSERM UMRS-1149, Facult\u00e9 de M\u00e9decine Xavier Bichat, Paris, France"},{"name":"CNRS ERL-8252, Centre de Recherche sur l\u2019Inflammation, Paris, France"},{"name":"Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9, Laboratoire d\u2019Excellence 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