Characterization of localized macrophages in bronchiolitis obliterans after allogeneic hematopoietic cell transplantation

Taiga Kuroi, Nobuharu Fujii, Koichi Ichimura, Keisuke Seike, Akira Yamamoto, Yui Kambara, Seiichiro Sugimoto, Shinji Otani, Kyosuke Saeki, Hideaki Fujiwara, Hisakazu Nishiomori, Takahiro Oto, Yoshinobu Maeda

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Bronchiolitis obliterans syndrome (BOS) remains one of the most devastating manifestations of chronic graft-versus-host disease in hematopoietic cell transplantation (HCT). Recent findings of BOS after lung transplantation indicate that donor (lung)-derived lung-resident macrophages contribute to BOS, suggesting that differences in the origin of immune cells and localized antigen-presenting cells cause the onset of BOS. Methods: We identified the phenotype and origin of infiltrating macrophages using immunohistochemistry and fluorescence in situ hybridization in eight sex-mismatched HCT recipients who underwent lung transplantation for BOS after HCT. Results: Most of the infiltrating macrophages appeared to be derived from donor (hematopoietic) cells in patients who developed BOS following HCT. Macrophages observed in the early-stage region of BOS were positive for cluster of differentiation (CD)68 and inducible nitric oxide synthase (iNOS) and negative for CD163 and CD206, suggesting an M1 phenotype. In the late-stage region, macrophages were negative for CD68 and iNOS in all patients, but also positive for CD163 and CD206 in some patients. Conclusions: Donor-derived M1-macrophages may be involved in the pathogenesis of the early-stage region of BOS. In addition, some macrophages in the late-stage region showed M2 polarization that might be involved in fibrosis.

Original languageEnglish
Pages (from-to)701-708
Number of pages8
JournalInternational journal of hematology
Volume114
Issue number6
DOIs
Publication statusAccepted/In press - 2021
Externally publishedYes

Keywords

  • Allogeneic hematopoietic cell transplantation
  • Bronchiolitis obliterans syndrome
  • Graft-versus-host disease
  • Lung transplantation
  • Macrophage

ASJC Scopus subject areas

  • Hematology

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