Bioinspired carbon monoxide delivery using artificial blood attenuates the progression of obliterative bronchiolitis via suppression of macrophage activation by IL-17A.

Abstract

Carbon monoxide (CO) is expected to attenuate the progression of obliterative bronchiolitis (OB), which is a serious complication after lung transplantation. However, issues in terms of feasible exogenous CO supply, such as continuousness and safety, remain unsolved. Here, we applied nano red blood cells, namely hemoglobin vesicles (Hb-V), as a CO cargo based on the biomimetic concept and investigated the therapeutic potential of CO-loaded Hb-V on OB in orthotopic tracheal transplant model mice. The CO-loaded Hb-V was comprised of negatively charged liposomes encapsulating carbonylhemoglobin with a size of ca. 220 nm. The results of histological evaluation showed that allograft luminal occlusion and fibrosis were significantly ameliorated by treatment with CO-loaded Hb-V compared to treatment with saline, cyclosporine, and Hb-V. The therapeutic effects of CO-loaded Hb-V on OB were due to the suppression of M1 macrophage activation in tracheal allografts, resulting from decreased IL-17A production. Furthermore, the expression of TNF-α and TGF-β in tracheal allografts was decreased by CO-loaded Hb-V treatment but not saline and Hb-V treatment, indicating that CO liberated from CO-loaded Hb-V inhibits epithelial-mesenchymal transition. These findings suggest that CO-loaded Hb-V exerts strong therapeutic efficacy against OB via the regulation of macrophage activation by IL-17A and TGF-β-driven epithelial-mesenchymal transition.

• Authors: Yuki Watabe, Kazuaki Taguchi, Hiromi Sakai, Yuki Enoki, Toru Maruyama, Masaki Otagiri, Mitsutomo Kohno, Kazuaki Matsumoto
• Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 170 Pg. 43-51 (Jan 2022) ISSN: 1873-3441 [Electronic] Netherlands
• PMID: 34864198 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Blood Substitutes
• Hemoglobins
• Interleukin-17
• Liposomes
• Transforming Growth Factor beta
• Carbon Monoxide

Topics

• Animals
• Blood Substitutes (administration & dosage, pharmacology)
• Bronchiolitis Obliterans (drug therapy)
• Carbon Monoxide (administration & dosage, pharmacology)
• Disease Models, Animal
• Disease Progression
• Drug Delivery Systems
• Epithelial-Mesenchymal Transition
• Hemoglobins (pharmacology)
• Interleukin-17 (metabolism)
• Liposomes
• Macrophage Activation
• Mice
• Mice, Inbred C57BL
• Trachea (transplantation)
• Transforming Growth Factor beta (metabolism)