{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:35:25Z","timestamp":1790645725547,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Reims-Metropole"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In inflammatory diseases, polymorphonuclear neutrophils (PMNs) are known to produce elevated levels of pro-inflammatory cytokines and proteases. To limit ensuing exacerbated cell responses and tissue damage, novel therapeutic agents are sought. 4aa and 4ba, two pyridazinone-scaffold-based phosphodiesterase-IV inhibitors are compared in vitro to zardaverine for their ability to: (1) modulate production of pro-inflammatory mediators, reactive oxygen species (ROS), and phagocytosis; (2) modulate degranulation by PMNs after transepithelial lung migration. Compound 4ba and zardaverine were tested in vivo for their ability to limit tissue recruitment of PMNs in a murine air pouch model. In vitro treatment of lipopolysaccharide-stimulated PMNs with compounds 4aa and 4ba inhibited the release of interleukin-8, tumor necrosis factor-\u03b1, and matrix metalloproteinase-9. PMNs phagocytic ability, but not ROS production, was reduced following treatment. Using a lung inflammation model, we proved that PMNs transmigration led to reduced expression of the CD16 phagocytic receptor, which was significantly blunted after treatment with compound 4ba or zardaverine. Using the murine air pouch model, LPS-induced PMNs recruitment was significantly decreased upon addition of compound 4ba or zardaverine. Our data suggest that new pyridazinone derivatives have therapeutic potential in inflammatory diseases by limiting tissue recruitment and activation of PMNs.<\/jats:p>","DOI":"10.3390\/ijms23137226","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T20:47:56Z","timestamp":1656535676000},"page":"7226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inhibition of Recruitment and Activation of Neutrophils by Pyridazinone-Scaffold-Based Compounds"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1187-956X","authenticated-orcid":false,"given":"Aur\u00e9lie","family":"Moniot","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Reims Champagne-Ardenne, EA 4691 BIOS, 51 Rue Cognacq Jay, 51100 Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1927-9801","authenticated-orcid":false,"given":"Julien","family":"Braux","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Reims Champagne-Ardenne, EA 4691 BIOS, 51 Rue Cognacq Jay, 51100 Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5438-8416","authenticated-orcid":false,"given":"Renaud","family":"Siboni","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Reims Champagne-Ardenne, EA 4691 BIOS, 51 Rue Cognacq Jay, 51100 Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Guillaume","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Reims Champagne-Ardenne, EA 4691 BIOS, 51 Rue Cognacq Jay, 51100 Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4708-1034","authenticated-orcid":false,"given":"Sandra","family":"Audonnet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Reims Champagne-Ardenne, URCACyt, 51 Rue Cognacq Jay, 51100 Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Allart-Simon","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Reims Champagne-Ardenne, UMR CNRS 7312 ICMR, 51 Rue Cognacq Jay, 51100 Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1947-3858","authenticated-orcid":false,"given":"Janos","family":"Sapi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Reims Champagne-Ardenne, UMR CNRS 7312 ICMR, 51 Rue Cognacq Jay, 51100 Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3526-9985","authenticated-orcid":false,"given":"Rabindra","family":"Tirouvanziam","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Center for CF and Airways Disease Research, Children\u2019s Healthcare of Atlanta, 2015 Uppergate Road, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8307-9986","authenticated-orcid":false,"given":"St\u00e9phane","family":"G\u00e9rard","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Reims Champagne-Ardenne, UMR CNRS 7312 ICMR, 51 Rue Cognacq Jay, 51100 Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2651-9372","authenticated-orcid":false,"given":"Sophie C.","family":"Gangloff","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Reims Champagne-Ardenne, EA 4691 BIOS, 51 Rue Cognacq Jay, 51100 Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4826-2160","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Velard","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Reims Champagne-Ardenne, EA 4691 BIOS, 51 Rue Cognacq Jay, 51100 Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/j.micinf.2003.09.008","article-title":"Neutrophil granules and secretory vesicles in inflammation","volume":"5","author":"Faurschou","year":"2003","journal-title":"Microbes Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev-pathol-020712-164023","article-title":"The Multifaceted Functions of Neutrophils","volume":"9","author":"Mayadas","year":"2014","journal-title":"Annu. 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