Work

Donor-derived eosinophils contribute to ischemia-reperfusion injury of the lung allograft in an iNOS-dependent fashion 2983

Year: 2025

Type: article

Abstract: Description Despite advances in preservation techniques, approximately 15% of lung transplant recipients experience complications due to ischemia-reperfusion injury (IRI). IRI is a complex inflammatory condition involving rapid oxidative stress, which ultimately leads to lung damage and dysfunction, potentiating both acute and chronic rejection. It is known that reactive oxygen species produced by inducible nitric oxide synthase (iNOS) can damage lung parenchymal tissue. Thus, we evaluated the phenotype of the iNOS-expressing cells in resting lungs and those subject to storage in Perfadex® preservation solution. In resting lungs, roughly 2/3 of the iNOS-expressing cells consisted of myeloid cells, with 1/3 expressing markers of eosinophils. After cold storage in Perfadex® preservation solution, eosinophils became the dominant iNOS-producing cell in the lung (>75% of iNOS cells). To explore the involvement of eosinophil-derived iNOS in lung IRI, eosinophil-sufficient and deficient grafts were preserved in Perfadex® storage, followed by implantation. Comparable to human data, donor-derived eosinophils demonstrated signs of activation as measured by CD69, CD63 and CD107a and expressed high levels of iNOS. Depleting donor eosinophils or inhibiting donor-derived iNOS by adding L-N6-(1-Iminoethyl) lysine dihydrochloride (LNIL) to the preservation solution improved oxygenation. Thus, targeting eosinophil-derived iNOS could significantly enhance transplant outcomes. Funding Sources NIH R01AI145108-01 NIH PO1 AI116501 Topic Categories Transplantation Immunology (TRAN)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.833