{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T12:20:35Z","timestamp":1788178835240,"version":"build-2803163510"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Acute respiratory distress syndrome (ARDS) may remain regionally permeable and poorly reparative after the initiating insult has weakened. We propose that, in a biologically enriched subset of non-resolving ARDS, repeated entry of circulating apolipoprotein B-containing triglyceride-rich lipoproteins (ApoB-TRLs) into an injured perivascular or interstitial compartment provides a renewable substrate for local injury. Catalytically active lipoprotein lipase (LPL) converts particle triglyceride (TG) to free fatty acids (FFAs). When FFA generation exceeds albumin buffering, cellular disposal, and lymphatic removal, redox and lipid-mediator signaling induces a focused cytokine program and recruits neutrophils. Oxidants, proteases, and neutrophil extracellular trap (NET)-fibrin complexes then injure the glycocalyx, junctions, matrix, and epithelium, permitting entry of the next particle cohort. Renewed source-resolved input, rather than lipid abundance alone, distinguishes a self-maintaining loop from a finite amplifier. Effective LPL activity, a macrophage brake, regional hypoxia, and slow structural locks modify circuit phase and reversibility but do not define loop closure. Spatial progression is predicted to be signal-first: mobile inflammatory or coagulation relays prime a remote endothelial gate, while fresh substrate is supplied by the recipient microcirculation. The decisive prediction is ordered recurrence in the same microdomain: source-resolved entry and conversion precede inflammatory execution and barrier loss, and interrupting a verified downstream executor after matching the first input prevents a second particle input. Failure of this sequence would narrow or reject the hypothesis.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1859209","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T12:11:11Z","timestamp":1788178271000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Source-renewing ectopic ApoB-TRL lipolysis in non-resolving ARDS: a testable spatial hypothesis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuwu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Guangyuan Central Hospital","place":["Guangyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Guangyuan Central Hospital","place":["Guangyuan, 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