Multilamellated Basement Membranes in the Capillary Network of Alveolar Capillary Dysplasia.

Autor:	Kamp JC; Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany. Electronic address: kamp.jan-christopher@mh-hannover.de., Neubert L; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; Institute of Pathology, Hannover Medical School, Hannover, Germany., Schupp JC; Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut., Braubach P; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; Institute of Pathology, Hannover Medical School, Hannover, Germany., Wrede C; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany; Research Core Unit Electron Microscopy, Hannover Medical School, Hannover, Germany., Laenger F; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; Institute of Pathology, Hannover Medical School, Hannover, Germany., Salditt T; Institute of X-Ray Physics, University of Göttingen, Göttingen, Germany., Reichmann J; Institute of X-Ray Physics, University of Göttingen, Göttingen, Germany., Welte T; Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany., Ruhparwar A; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany., Ius F; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany., Schwerk N; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; Clinic for Pediatric Pneumology, Allergology, and Neonatology, Hannover Medical School, Hannover, Germany., Bergmann AK; Institute of Human Genetics, Hannover Medical School, Hannover, Germany., von Hardenberg S; Institute of Human Genetics, Hannover Medical School, Hannover, Germany., Griese M; Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital of Ludwig Maximilian University Munich, German Center for Lung Research, Munich, Germany., Rapp C; Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital of Ludwig Maximilian University Munich, German Center for Lung Research, Munich, Germany., Olsson KM; Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany., Fuge J; Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany., Park DH; Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany., Hoeper MM; Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany., Jonigk DD; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; Institute of Pathology, University of Aachen, Aachen, Germany., Knudsen L; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany., Kuehnel MP; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; Institute of Pathology, University of Aachen, Aachen, Germany.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2024 Feb; Vol. 194 (2), pp. 180-194. Date of Electronic Publication: 2023 Nov 27.
DOI:	10.1016/j.ajpath.2023.10.012
Abstrakt:	A minimal diffusion barrier is key to the pulmonary gas exchange. In alveolar capillary dysplasia (ACD), a rare genetically driven disease of early infancy, this crucial fibrovascular interface is compromised while the underlying pathophysiology is insufficiently understood. Recent in-depth analyses of vascular alterations in adult lung disease encouraged researchers to extend these studies to ACD and compare the changes of the microvasculature. Lung tissue samples of children with ACD (n = 12), adults with non-specific interstitial pneumonia (n = 12), and controls (n = 20) were studied using transmission electron microscopy, single-gene sequencing, immunostaining, exome sequencing, and broad transcriptome profiling. In ACD, pulmonary capillary basement membranes were hypertrophied, thickened, and multilamellated. Transcriptome profiling revealed increased CDH5, COL4A1, COL15A1, PTK2B, and FN1 and decreased VIT expression, confirmed by immunohistochemistry. In contrast, non-specific interstitial pneumonia samples showed a regular basement membrane architecture with preserved VIT expression but also increased COL15A1 + vessels. This study provides insight into the ultrastructure and pathophysiology of ACD. The lack of normally developed lung capillaries appeared to cause a replacement by COL15A1 + vessels, a mechanism recently described in interstitial lung disease. The VIT loss and FN1 overexpression might contribute to the unique appearance of basement membranes in ACD. Future studies are needed to explore the therapeutic potential of down-regulating the expression of FN1 and balancing VIT deficiency. Competing Interests: Disclosure Statement J.C.S. received fees for lectures from Boehringer Ingelheim and Kinevant, all outside the present study. T.W. declares funding by the German Ministry of Research and Education. M.M.H. received fees for lectures and consultations from Acceleron, Actelion, AOP, Bayer, Janssen, MSD, and Pfizer, all outside the present study. J.F. received personal fees/speaker honoraria from AstraZeneca, outside the submitted work. M.G. received fees for lectures from Boehringer Ingelheim, participates in an adjudication board in a nintedanib clinical trial, and received a research grant from Boehringer Ingelheim. D.D.J. received fees for lectures from Boehringer Ingelheim and declares a research contract with Boehringer Ingelheim (contract number 43099358). All other authors declare no existing conflicts of interest. (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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