{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:50:29Z","timestamp":1790747429999,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0D6817N"],"award-info":[{"award-number":["G0D6817N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Neutrophil overstimulation plays a crucial role in tissue damage during severe infections. Because pathogen\u2010derived neuraminidase (NEU) stimulates neutrophils, we investigated whether host NEU can be targeted to regulate the neutrophil dysregulation observed in severe infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>The effects of NEU inhibitors on lipopolysaccharide (LPS)\u2010stimulated neutrophils from healthy donors or COVID\u201019 patients were determined by evaluating the shedding of surface sialic acids, cell activation, and reactive oxygen species (ROS) production. Re\u2010analysis of single\u2010cell RNA sequencing of respiratory tract samples from COVID\u201019 patients also was carried out. The effects of oseltamivir on sepsis and betacoronavirus\u2010induced acute lung injury were evaluated in murine models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Oseltamivir and zanamivir constrained host NEU activity, surface sialic acid release, cell activation, and ROS production by LPS\u2010activated human neutrophils. Mechanistically, LPS increased the interaction of NEU1 with matrix metalloproteinase 9 (MMP\u20109). Inhibition of MMP\u20109 prevented LPS\u2010induced NEU activity and neutrophil response. In vivo, treatment with oseltamivir fine\u2010tuned neutrophil migration and improved infection control as well as host survival in peritonitis and pneumonia sepsis. NEU1 also is highly expressed in neutrophils from COVID\u201019 patients, and treatment of whole\u2010blood samples from these patients with either oseltamivir or zanamivir reduced neutrophil overactivation. Oseltamivir treatment of intranasally infected mice with the mouse hepatitis coronavirus 3 (MHV\u20103) decreased lung neutrophil infiltration, viral load, and tissue damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>These findings suggest that interplay of NEU1\u2013MMP\u20109 induces neutrophil overactivation. In vivo, NEU may serve as a host\u2010directed target to dampen neutrophil dysfunction during severe infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.16013","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T20:17:09Z","timestamp":1671221829000},"page":"1460-1481","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Neuraminidase is a host\u2010directed approach to regulate neutrophil responses in sepsis and COVID\u201019"],"prefix":"10.1111","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5475-0067","authenticated-orcid":false,"given":"Rodrigo","family":"de Oliveira Formiga","sequence":"first","affiliation":[{"name":"Department of Pharmacology Federal University of Santa Catarina  Florian\u00f3polis Brazil"},{"name":"Universit\u00e9 de Paris, Institut Cochin, INSERM U1016, CNRS  Paris France"},{"name":"Laboratory of Immunobiology, Department of Microbiology, Immunology and Parasitology Federal University of Santa Catarina  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via C.","family":"Amaral","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Federal University of Santa Catarina  Florian\u00f3polis Brazil"},{"name":"Laboratory of Immunobiology, Department of Microbiology, Immunology and Parasitology Federal University of Santa Catarina  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila F.","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Federal University of Santa Catarina  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A. 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