Z Geburtshilfe Neonatol 2023; 227(03): e38-e39
DOI: 10.1055/s-0043-1769248
Abstracts
Freie Vorträge
BPD & Sauerstoff

CXCL10 deficiency protects from lung macrophage invasion and enables lung growth during acute injury and recovery in experimental bronchopulmonary dysplasia

Dharmesh Hirani
1   University of Cologne and Universities of Giessen and Marburg Lung Center (UGMLC), Translational Experimental Pediatrics, Experimental Pneumology, Center for Molecular Medicine Cologne (CMMC), University of Cologne; Institute for Lung Health (ILH) and Cardio-Pulmonary Institute (CPI), Köln-Gießen, Germany
,
Florian Thielen
2   University of Cologne, Translational Experimental Pediatrics, Experimental Pneumology, Department of Pediatric and Adolescent Medicine, University Hospital Cologne, Faculty of Medicine, Köln, Germany
,
Siavash Mansouri
3   Max-Planck-Institute for Heart and Lung Research, Department of Lung Development and Remodeling, Member of the German Center for Lung Research (DZL), Bad Nauheim, Germany
,
Soula Danopoulos
4   University of California, Los Angeles, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States
,
Christina Vohlen
2   University of Cologne, Translational Experimental Pediatrics, Experimental Pneumology, Department of Pediatric and Adolescent Medicine, University Hospital Cologne, Faculty of Medicine, Köln, Germany
,
Pinar Haznedar-Karakaya
2   University of Cologne, Translational Experimental Pediatrics, Experimental Pneumology, Department of Pediatric and Adolescent Medicine, University Hospital Cologne, Faculty of Medicine, Köln, Germany
,
Jasmine Mohr
2   University of Cologne, Translational Experimental Pediatrics, Experimental Pneumology, Department of Pediatric and Adolescent Medicine, University Hospital Cologne, Faculty of Medicine, Köln, Germany
,
Rebecca Wilke
2   University of Cologne, Translational Experimental Pediatrics, Experimental Pneumology, Department of Pediatric and Adolescent Medicine, University Hospital Cologne, Faculty of Medicine, Köln, Germany
,
Jaco Selle
2   University of Cologne, Translational Experimental Pediatrics, Experimental Pneumology, Department of Pediatric and Adolescent Medicine, University Hospital Cologne, Faculty of Medicine, Köln, Germany
,
Ivana Mizikóva
2   University of Cologne, Translational Experimental Pediatrics, Experimental Pneumology, Department of Pediatric and Adolescent Medicine, University Hospital Cologne, Faculty of Medicine, Köln, Germany
,
Margarete Odenthal
5   University of Cologne, Center for Molecular Medicine Cologne (CMMC) and Institute for Pathology, University Hospital Cologne, Faculty of Medicine, Köln, Germany
,
Cristina M. Alvira
6   Stanford University, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, , United States
,
Celien Kuiper-Makris
2   University of Cologne, Translational Experimental Pediatrics, Experimental Pneumology, Department of Pediatric and Adolescent Medicine, University Hospital Cologne, Faculty of Medicine, Köln, Germany
,
Gloria S. Pryhuber
7   University of Rochester Medical Center, Division of Neonatology, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY , United States
,
Christian Pallasch
8   University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology (CIO) Köln-Bonn, Köln, Germany
,
Silke Koningsbruggen-Rietschel
9   University of Cologne, Department of Pediatric and Adolescent Medicine, University Hospital Cologne, Faculty of Medicine, Köln, Germany
,
Denise Al-Alam
4   University of California, Los Angeles, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States
,
Werner Seeger
10   Universities of Giessen and Marburg Lung Center (UGMLC), Institute for Lung Health (ILH) and Cardio-Pulmonary Institute (CPI), Max-Planck-Institute for Heart and Lung Research, member of the German Center for Lung Research (DZL), Gießen, Germany
,
Jörg Dötsch
9   University of Cologne, Department of Pediatric and Adolescent Medicine, University Hospital Cologne, Faculty of Medicine, Köln, Germany
,
Rajkumar Savai
10   Universities of Giessen and Marburg Lung Center (UGMLC), Institute for Lung Health (ILH) and Cardio-Pulmonary Institute (CPI), Max-Planck-Institute for Heart and Lung Research, member of the German Center for Lung Research (DZL), Gießen, Germany
,
Miguel A. Alejandre Alcazar
11   University of Cologne and Universities of Giessen and Marburg Lung Center (UGMLC),Translational Experimental Pediatrics, Experimental Pneumology, Center for Molecular Medicine Cologne (CMMC), Cologne Excellence Cluster on Stress Responses in Aging-associated Diseases (CECAD); Institute for Lung Health (ILH), Cardio-Pulmonary Institute (CPI), Köln-Gießen, Germany
› Institutsangaben
› Weitere Informationen
Auch verfügbar aufeRef
 
 

    Rationale Preterm infants with oxygen supplementation frequently develop a chronic lung disease known as bronchopulmonary dysplasia (BPD). Pathomechanistically, an inflammatory response with increased migration and activation of macrophages plays a major role. Elevated levels of CXCL10 (C-X-C motif chemokine ligand 10), which has chemotactic and activating effects on proinflammatory inflammatory cells, were detected in lungs of infants evolving BPD. Therefore, we investigated whether CXCL10 deficiency protects newborn mice from hyperoxia-induced lung injury (as a model of BPD).

    Methods (1) Homozygous CXCL10 knockout (CXCL10-/-) mice as well as wild-type mice (WT) were either exposed to hyperoxia (85% O2, HYX) or normoxia (21% O2, NOX) from postnatal day 1 (P1) to P14 and studied at P14. (2) For recovery, some mice were transferred from HYX to NOX for two additional weeks and were then sacrificed at P28. Excised lungs were snap-frozen for molecular biology studies or pressure-fixed with paraformaldehyde and embedded in paraffin for histomorphometric analyses. (3) J744A.1 macrophages were treated with CXCL10 or CXCR3 antagonist, and cell migration was studied.

    Results (1). Lungs of HYX-exposed WT showed significantly increased macrophage invasion at P14 compared with the control group. This inflammatory response after HYX resulted in impaired alveolarization, increased apoptosis and extracellular matrix (ECM) remodeling. CXCL10-/- protected the newborn mice from the inflammation and partially from the HYX-induced structural changes. (2) After recovery at P28, CXCL10-/- mice exhibited improved lung structure and attenuated matrix remodeling in comparison to WT. (3) Loss of CXCL10 prevented the macrophage influx to the lungs at both P14 and P28 after HYX. (3) Mouse and human macrophages treated with recombinant CXCL10 or CXCR3 antagonist significantly increased and reduced migration, respectively.

    Conclusion Our data demonstrate that deficiency of CXCR3-CXCL10 axis blocks macrophage chemotaxis to the lung, partially enables lung growth, and protects from ECM in experimental BPD.


     

    Interessenkonflikt

    Es bestehen keine Interessenkonflikte.

    Publikationsverlauf

    Artikel online veröffentlicht:
    06. Juni 2023

    © 2023. Thieme. All rights reserved.

    Georg Thieme Verlag KG
    Rüdigerstraße 14, 70469 Stuttgart, Germany