{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:58:59Z","timestamp":1788537539884,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 ES025191"],"award-info":[{"award-number":["RO1 ES025191"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIESH","award":["P30ES025128"],"award-info":[{"award-number":["P30ES025128"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The use of carbon nanotubes has increased in the past few decades. Carbon nanotubes are implicated in the pathogenesis of pulmonary sarcoidosis, a chronic granulomatous inflammatory condition. We developed a murine model of chronic granulomatous inflammation using multiwall carbon nanotubes (MWCNT) to investigate mechanisms of granuloma formation. Using this model, we demonstrated that myeloid deficiency of ATP-binding cassette (ABC) cholesterol transporter (ABCG1) promotes granuloma formation and fibrosis with MWCNT instillation; however, the mechanism remains unclear. Our previous studies showed that MWCNT induced apoptosis in bronchoalveolar lavage (BAL) cells of wild-type (C57BL\/6) mice. Given that continual apoptosis causes persistent severe lung inflammation, we hypothesized that ABCG1 deficiency would increase MWCNT-induced apoptosis thereby promoting granulomatous inflammation and fibrosis. To test our hypothesis, we utilized myeloid-specific ABCG1 knockout (ABCG1 KO) mice. Our results demonstrate that MWCNT instillation enhances pulmonary fibrosis in ABCG1 KO mice compared to wild-type controls. Enhanced fibrosis is indicated by increased trichrome staining and transforming growth factor-beta (TGF-\u03b2) expression in lungs, together with an increased expression of TGF-\u03b2 related signaling molecules, interleukin-13 (IL-13) and Smad-3. MWCNT induced more apoptosis in BAL cells of ABCG1 KO mice. Initiation of apoptosis is most likely mediated by the extrinsic pathway since caspase 8 activity and Fas expression are significantly higher in MWCNT instilled ABCG1 KO mice compared to the wild type. In addition, TUNEL staining shows that ABCG1 KO mice instilled with MWCNT have a higher percentage of TUNEL positive BAL cells and more efferocytosis than the WT control. Furthermore, BAL cells of ABCG1 KO mice instilled with MWCNT exhibit an increase in efferocytosis markers, milk fat globule-EGF factor 8 (MFG-E8) and integrin \u03b23. Therefore, our observations suggest that ABCG1 deficiency promotes pulmonary fibrosis by MWCNT, and this effect may be due to an increase in apoptosis and efferocytosis in BAL cells.<\/jats:p>","DOI":"10.3390\/ijms23010047","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T01:08:09Z","timestamp":1640135289000},"page":"47","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Myeloid ABCG1 Deficiency Enhances Apoptosis and Initiates Efferocytosis in Bronchoalveolar Lavage Cells of Murine Multi-Walled Carbon Nanotube-Induced Granuloma Model"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2592-7622","authenticated-orcid":false,"given":"Eman","family":"Soliman","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Bhalla","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed E. M.","family":"Elhassanny","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anagha","family":"Malur","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ogburn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Leffler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achut G.","family":"Malur","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, St. George\u2019s University, St. George 999166, Grenada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Jane","family":"Thomassen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1289\/ehp.0901159","article-title":"Case report: Lung disease in World Trade Center responders exposed to dust and smoke: Carbon nanotubes found in the lungs of World Trade Center patients and dust samples","volume":"118","author":"Wu","year":"2010","journal-title":"Environ. 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