التفاصيل البيبلوغرافية
| العنوان: |
Bronchoalveolar lavage (BAL) cells in idiopathic pulmonary fibrosis express a complex pro-inflammatory, pro-repair, angiogenic activation pattern, likely associated with macrophage iron accumulation. |
| المؤلفون: |
Lee, Jungnam, Arisi, Ivan, Puxeddu, Ermanno, Mramba, Lazarus K., Amicosante, Massimo, Swaisgood, Carmen M., Pallante, Marco, Brantly, Mark L., Sköld, C. Magnus, Saltini, Cesare |
| المصدر: |
PLoS ONE; 4/12/2018, Vol. 13 Issue 4, p1-15, 15p |
| مصطلحات موضوعية: |
IDIOPATHIC pulmonary fibrosis, BRONCHOALVEOLAR lavage, ANGIOGENIN, TISSUE remodeling, MACROPHAGE activation, DEVELOPMENTAL biology |
| مستخلص: |
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown cause characterized by alveolar epithelial damage, patchy interstitial fibrosis and diffuse microvascular abnormalities. In IPF, alveolar clustering of iron-laden alveolar macrophages—a common sign of microhemorrhage, has been associated with vascular abnormalities and worsening of pulmonary hypertension. As iron-dependent ROS generation has been shown to induce unrestrained macrophage activation in disease models of vascular damage, we explored alveolar macrophage activation phenotype in IPF patients (n = 16) and healthy controls (CTR, n = 7) by RNA sequencing of bronchoalveolar lavage (BAL) cells. The frequencies of macrophages in BAL cells were 86+4% and 83.4+8% in IPF and CTR groups, respectively (p-value = 0.41). In IPF patients, BAL cells showed increased iron-dependent ROS generation (p-value<0.05 vs CTR). Gene expression analysis showed overrepresentation of Gene Ontology processes/functions and KEGG pathways enriched in upregulated M1-type inflammatory (p-value<0.01), M2-type anti-inflammatory/tissue remodeling (p-value<0.0001), and MTPP-type chronic inflammatory/angiogenic (p-value<0.0001) chemokine and cytokine genes. The ex vivo finding was confirmed by the induction of iron-dependent ROS generation and chemokine/cytokine overexpression of Ccl4, Cxcl10 (M1), Il1rn (M2), Cxcl2, and Cxcl7 (MTPP) in MH-S murine immortalized alveolar macrophages exposed to ferric ammonium citrate in culture (p-value<0.05 vs CTR). The data show alveolar macrophage expression of a pro-inflammatory, tissue remodeling and angiogenic complex activation pattern, suggesting that iron accumulation may play a role in macrophage activation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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