Suppression of Neutrophil Antimicrobial Functions by Total Particulate Matter From Cigarette Smoke

dc.contributor.authorZhang, Yaoen
dc.contributor.authorGeng, Shuoen
dc.contributor.authorPrasad, G.L.en
dc.contributor.authorLi, Liwuen
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2019-08-29T12:25:42Zen
dc.date.available2019-08-29T12:25:42Zen
dc.date.issued2018-10-04en
dc.description.abstractChronic cigarette smoking is widely known to alter immune functions and compromise host defense against microbial infection. Neutrophils play an essential role in the immune defense against microbial pathogens and also participate in the development of the inflammatory responses. However, there is limited information about the effects of cigarette smoking on neutrophil response. In this study, cultured bonemarrow neutrophils were exposed to total particulate matter (TPM) from cigarette smoke. We found that TPM not only reduced LPS-induced TNFa production, but also suppressed neutrophil bactericidal activity. We also observed that TPM priming reduced the expression of NADPH oxidase component gp91 and iNOS, molecules important for bacterial killing. Mechanistically, we documented that TPM-primed neutrophils have reduced STAT1 activation following subsequent LPS challenge. STAT1 is a key transcription factor responsible for the expression of inflammatory genes as well as gp91 and iNOS. Collectively, reduced STAT1 activation and reduced NADPH oxidase/iNOS may potentially explain the compromised anti-microbial function of TPM-programmed neutrophils. Taken together, our findings reveal that the key innate immune neutrophil is subject to reprogramming by smoking to adopt an immune-suppressed state, potentially responsible for chronic smoking-mediated immunosuppression.en
dc.description.sponsorshipR. J. Reynolds Tobacco Companyen
dc.format.extent9 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationZhang Y, Geng S, Prasad GL and Li L (2018) Suppression of Neutrophil Antimicrobial Functions by Total Particulate Matter From Cigarette Smoke. Front. Immunol. 9:2274. doi: 10.3389/fimmu.2018.02274en
dc.identifier.doihttps://doi.org/10.3389/fimmu.2018.02274en
dc.identifier.urihttp://hdl.handle.net/10919/93293en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherFrontiersen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectneutrophil programmingen
dc.subjectTPMen
dc.subjectimmune-modulationen
dc.subjectNADPH oxidaseen
dc.subjectinflammationen
dc.titleSuppression of Neutrophil Antimicrobial Functions by Total Particulate Matter From Cigarette Smokeen
dc.title.serialFrontiers in Immunologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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