Predominance of M2 macrophages in organized thrombi in chronic thromboembolic pulmonary hypertension patients

Thomas Koudstaal*, Thierry van den Bosch, Ingrid Bergen, Karishma Lila, Paul Bresser, Harm Jan Bogaard, Karin Boomars, Rudi Hendriks, Jan von der Thüsen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease characterized by thrombotic occlusion of pulmonary arteries and vasculopathy, leading to increased pulmonary vascular resistance and progressive right-sided heart failure. Thrombotic lesions in CTEPH contain CD68+ macrophages, and increasing evidence supports their role in disease pathogenesis. Macrophages are classically divided into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages, which are involved in wound healing and tissue repair. Currently, the phenotype of macrophages and their localization within thrombotic lesions of CTEPH are largely unknown. In our study, we subclassified thrombotic lesions of CTEPH patients into developing fresh thrombi (FT) and organized thrombi (OT), based on the degree of fibrosis and remodeling. We used multiplex immunofluorescence histology to identify immune cell infiltrates in thrombotic lesions of CPTEH patients. Utilizing software-assisted cell detection and quantification, increased proportions of macrophages were observed in immune cell infiltrates of OT lesions, compared with FT. Strikingly, the proportions with a CD206+INOS M2 phenotype were significantly higher in OT than in FT, which mainly contained unpolarized macrophages. Taken together, we observed a shift from unpolarized macrophages in FT toward an expanded population of M2 macrophages in OT, indicating a dynamic role of macrophages during CTEPH pathogenesis.

Original languageEnglish
Article number2350670
JournalEuropean Journal of Immunology
Volume54
Issue number6
DOIs
Publication statusPublished - Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

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