Academic Journal
CXCL10 deficiency limits macrophage infiltration, preserves lung matrix, and enables lung growth in bronchopulmonary dysplasia
| العنوان: | CXCL10 deficiency limits macrophage infiltration, preserves lung matrix, and enables lung growth in bronchopulmonary dysplasia |
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| المؤلفون: | Hirani, Dharmesh V., Thielen, Florian, Mansouri, Siavash, Danopoulos, Soula, Vohlen, Christina, Haznedar-Karakaya, Pinar, Mohr, Jasmine, Wilke, Rebecca, Selle, Jaco, Grosch, Thomas, Mizik, Ivana, Odenthal, Margarete, Alvira, Cristina M., Kuiper-Makris, Celien, Pryhuber, Gloria S., Pallasch, Christian, van Koningsbruggen-Rietschel, S., Al-Alam, Denise, Seeger, Werner, Savai, Rajkumar, Dötsch, Jörg, Alejandre Alcazar, Miguel A. |
| المساهمون: | Deutsche Forschungsgemeinschaft, Marga und Walter Boll-Stiftung, Else Kröner-Fresenius-Stiftung, Center for Molecular Medicine Cologne, University of Cologne, Stiftung Oskar-Helene-Heim, NIH, NHLBI, Universitätsklinikum Köln |
| المصدر: | Inflammation and Regeneration ; volume 43, issue 1 ; ISSN 1880-8190 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| الوصف: | Preterm infants with oxygen supplementation are at high risk for bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease. Inflammation with macrophage activation is central to the pathogenesis of BPD. CXCL10, a chemotactic and pro-inflammatory chemokine, is elevated in the lungs of infants evolving BPD and in hyperoxia-based BPD in mice. Here, we tested if CXCL10 deficiency preserves lung growth after neonatal hyperoxia by preventing macrophage activation. To this end, we exposed Cxcl10 knockout ( Cxcl10 −/− ) and wild-type mice to an experimental model of hyperoxia (85% O 2 )-induced neonatal lung injury and subsequent regeneration. In addition, cultured primary human macrophages and murine macrophages (J744A.1) were treated with CXCL10 and/or CXCR3 antagonist. Our transcriptomic analysis identified CXCL10 as a central hub in the inflammatory network of neonatal mouse lungs after hyperoxia. Quantitative histomorphometric analysis revealed that Cxcl10 −/− mice are in part protected from reduced alveolar. These findings were related to the preserved spatial distribution of elastic fibers, reduced collagen deposition, and protection from macrophage recruitment/infiltration to the lungs in Cxcl10 −/− mice during acute injury and regeneration. Complimentary, studies with cultured human and murine macrophages showed that hyperoxia induces Cxcl10 expression that in turn triggers M1-like activation and migration of macrophages through CXCR3. Finally, we demonstrated a temporal increase of macrophage-related CXCL10 in the lungs of infants with BPD. In conclusion, our data demonstrate macrophage-derived CXCL10 in experimental and clinical BPD that drives macrophage chemotaxis through CXCR3, causing pro-fibrotic lung remodeling and arrest of alveolarization. Thus, targeting the CXCL10-CXCR3 axis could offer a new therapeutic avenue for BPD. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s41232-023-00301-6 |
| DOI: | 10.1186/s41232-023-00301-6.pdf |
| DOI: | 10.1186/s41232-023-00301-6/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s41232-023-00301-6 https://link.springer.com/content/pdf/10.1186/s41232-023-00301-6.pdf https://link.springer.com/article/10.1186/s41232-023-00301-6/fulltext.html |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.CAC77ABD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s41232-023-00301-6 |
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