{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T22:06:32Z","timestamp":1771538792059,"version":"3.50.1"},"reference-count":44,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:p>Idiopathic pneumonia syndrome (IPS) is a significant cause of morbidity and mortality post-bone marrow transplantation (BMT) in humans. In our established murine IPS model in which lethally conditioned recipients are given allogeneic bone marrow and splenocytes, recruitment of host monocytes occurs early post-BMT, followed by donor T cells concomitant with development of severe lung dysfunction. Because matrix metalloproteinase 12 (MMP12) is important for macrophage infiltration and injury in other mouse models of lung disease such as emphysema, lethally conditioned MMP12<jats:sup>\u2212\/\u2212<\/jats:sup>mice were used as allogeneic recipients to determine whether MMP12 plays a similar role in potentiating lung injury in IPS. Surprisingly, MMP12<jats:sup>\u2212\/\u2212<\/jats:sup>mice developed IPS and exhibited an accelerated allogeneic T cell-dependent decrease in compliance compared with wild-type (WT) recipients. MMP12<jats:sup>\u2212\/\u2212<\/jats:sup>, but not WT, mice also had allogeneic T cell-dependent elevated lung resistance post-BMT. Recruitment of monocytes and T cells into the lungs was not altered on day 7 post-BMT, but the lungs of MMP12<jats:sup>\u2212\/\u2212<\/jats:sup>recipients had increased collagen deposition, a feature normally not seen in our IPS model. MMP12<jats:sup>\u2212\/\u2212<\/jats:sup>mice had a compensatory increase in MMP2 in the lungs post-BMT, as well as increased \u03b26-integrin compared with WT recipients, and only in the presence of allogeneic T cells. Levels of total transforming growth factor (TGF)-\u03b21 protein in the lungs were elevated compared with WT recipients, consistent with the profibrotic function of \u03b26-integrin as an activator of TGF-\u03b2. These data indicate that host-derived MMP12 may be important in limiting development of IPS by allowing proper remodeling of extracellular matrix and effective repair of BMT-related injury.<\/jats:p>","DOI":"10.1152\/ajplung.00383.2009","type":"journal-article","created":{"date-parts":[[2011,7,23]],"date-time":"2011-07-23T04:56:39Z","timestamp":1311396999000},"page":"L519-L526","source":"Crossref","is-referenced-by-count":14,"title":["Evidence for early fibrosis and increased airway resistance in bone marrow transplant recipient mice deficient in MMP12"],"prefix":"10.1152","volume":"301","author":[{"given":"Kristen A.","family":"England","sequence":"first","affiliation":[{"name":"Department of 1Pediatrics, Heme\/Onc\/BMT Division, University of Minnesota Cancer Center and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew P.","family":"Price","sequence":"additional","affiliation":[{"name":"Department of 1Pediatrics, Heme\/Onc\/BMT Division, University of Minnesota Cancer Center and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin V.","family":"Tram","sequence":"additional","affiliation":[{"name":"Department of 1Pediatrics, Heme\/Onc\/BMT Division, University of Minnesota Cancer Center and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven D.","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce R.","family":"Blazar","sequence":"additional","affiliation":[{"name":"Department of 1Pediatrics, Heme\/Onc\/BMT Division, University of Minnesota Cancer Center and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Panoskaltsis-Mortari","sequence":"additional","affiliation":[{"name":"Department of 1Pediatrics, Heme\/Onc\/BMT Division, University of Minnesota Cancer Center and"},{"name":"Pulmonary, Allergy &amp; 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