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Chronic PMN inflammation is a hallmark of COPD; however, the mechanisms driving chronic recruitment of PMNs into the lung are poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In this study, we tested the hypothesis that PMN-derived, NE+\u2009EVs can spawn additional NE+\u2009EVs and promote chronic PMN inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>NE+\u2009and NE- EVs were generated in vitro upon stimulation of isolated human neutrophils with N-Formylmethionyl-leucyl-phenylalanine or the matrikine proline-glycine-proline (PGP). Smoke EVs were isolated from mice exposed to cigarette smoke. EVs were transferred into na\u00efve mice and mouse PMN EVs were isolated 7\u2009days later. Serial transfers of mouse EVs into na\u00efve recipients were performed to determine the self-propagating nature of NE+\u2009EVs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and main results<\/jats:title>\n                    <jats:p>Activated human PMN\u2013derived (ie, CD66b+\/NE+) EVs, but not NE- EVs, elicited the de novo generation of murine PMN\u2013derived Ly6G+\/NE+\u2009EVs in recipient mouse airways. These Ly6G+\/NE+\u2009EVs serially propagated emphysema and de novo NE+\u2009EV production in multiple passages between new na\u00efve recipients. This process is driven by such mouse NE+\u2009EVs apparently generating PGP that causes both PMN influx into the airways and activation of the newly arrived PMNs to release yet more NE+\u2009EVs. Likewise, smoke-elicited EVs were able to serially propagate emphysema.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings have far-reaching implications for our understanding of COPD, chronic inflammation, and EVs as self-propagating agents in smokers and COPD patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajrccm\/aamag002","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T12:38:55Z","timestamp":1768394335000},"page":"746-756","source":"Crossref","is-referenced-by-count":3,"title":["Self-propagating nature of pathogenic extracellular vesicles associated with smoking and chronic obstructive pulmonary disease"],"prefix":"10.1093","volume":"212","author":[{"given":"Camilla","family":"Margaroli","sequence":"first","affiliation":[{"name":"Division of Molecular and Cellular Pathology, Department of Pathology, 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