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A novel model was developed to deliver a stimulation simulating a sneeze (55 mmHg for 50 ms) at 26\u00b0C to the apical surface of mouse and human nasal epithelial cells. Ciliary beating was visualized, and changes in ciliary beat frequency (CBF) were determined. To interrogate the molecular cascades driving sneeze\u2010induced changes of CBF, pharmacologic manipulation of intra\u2010 and extracellular calcium, purinergic, PKA, and nitric oxide (NO) signaling were performed. CBF rapidly increases by \u2265150% in response to a sneeze, which is dependent on the release of adenosine triphosphate (ATP), calcium influx, and PKA activation. Furthermore, apical release of ATP is independent of calcium influx, but calcium influx and subsequent increase in CBF are dependent on the ATP release. Lastly, we observed a blunted ciliary response in surgical specimens derived from patients with chronic rhinosinusitis compared to control patients. Apical ATP release with subsequent calcium mobilization and PKA activation are involved in sinonasal ciliary response to sneezing, which is blunted in patients with upper\u2010airway disease.\u2014Zhao, K.\u2010Q., Cowan, A. T., Lee, R. J., Goldstein, N., Droguett, K., Chen, B., Zheng, C., Villalon, M., Palmer, J. N., Kreindler, J. L., Cohen, N. A. Molecular modulation of airway epithelial ciliary response to sneezing.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 3178\u20133187 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-202184","type":"journal-article","created":{"date-parts":[[2012,4,19]],"date-time":"2012-04-19T20:14:29Z","timestamp":1334866469000},"page":"3178-3187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Molecular modulation of airway epithelial ciliary response to sneezing"],"prefix":"10.1096","volume":"26","author":[{"given":"Ke\u2010Qing","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery, Eye and Ear, Nose, and Throat Hospital, School of Shanghai Medicine Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T.","family":"Cowan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Temple University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Medical Science Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Droguett","sequence":"additional","affiliation":[{"name":"Department of Physiology Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunquan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery, Eye and Ear, Nose, and Throat Hospital, School of Shanghai Medicine Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Villalon","sequence":"additional","affiliation":[{"name":"Department of Physiology Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James N.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Kreindler","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia University of Pennsylvania School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics University of Pennsylvania School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Surgical Services Philadelphia Veterans Affairs Medical Center  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,4,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/137.3.726"},{"key":"e_1_2_7_3_1","first-page":"48","article-title":"The role of mucus in transport by cilia","volume":"102","author":"Eliezer N.","year":"1970","journal-title":"Am. 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