{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:03:15Z","timestamp":1789473795121,"version":"build-2803163510"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The host injury involved in multiorgan system failure during severe inflammation is mediated, in part, by massive infiltration and sequestration of hyperactive neutrophils in the visceral organ. A recombinant form of human activated protein C (rhAPC) has shown cytoprotective and anti-inflammatory functions in some clinical and animal studies, but the direct mechanism is not fully understood. Recently, we reported that, during endotoxemia and severe polymicrobial peritonitis, integrin VLA-3 (CD49c\/CD29) is specifically upregulated on hyperinflammatory neutrophils and that targeting the VLA-3high neutrophil subpopulation improved survival in mice. In this article, we report that rhAPC binds to human neutrophils via integrin VLA-3 (CD49c\/CD29) with a higher affinity compared with other Arg-Gly-Asp binding integrins. Similarly, there is preferential binding of activated protein C (PC) to Gr1highCD11bhighVLA-3high cells isolated from the bone marrow of septic mice. Furthermore, specific binding of rhAPC to human neutrophils via VLA-3 was inhibited by an antagonistic peptide (LXY2). In addition, genetically modified mutant activated PC, with a high affinity for VLA-3, shows significantly improved binding to neutrophils compared with wild-type activated PC and significantly reduced neutrophil infiltration into the lungs of septic mice. These data indicate that variants of activated PC have a stronger affinity for integrin VLA-3, which reveals novel therapeutic possibilities.<\/jats:p>","DOI":"10.4049\/jimmunol.1700541","type":"journal-article","created":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T03:14:36Z","timestamp":1504754076000},"page":"2930-2936","source":"Crossref","is-referenced-by-count":9,"title":["Activated Protein C Attenuates Severe Inflammation by Targeting VLA-3high Neutrophil Subpopulation in Mice"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7877-4802","authenticated-orcid":false,"given":"Pranita P","family":"Sarangi","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5428-8594","authenticated-orcid":false,"given":"Hyun-wook","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelena V","family":"Lerman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4518-0098","authenticated-orcid":false,"given":"Alissa","family":"Trzeciak","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1051-5521","authenticated-orcid":false,"given":"Eric J","family":"Harrower","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-0553","authenticated-orcid":false,"given":"Alireza R","family":"Rezaie","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, David H. 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