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Emphysema-associated Autoreactive Antibodies Exacerbate Post–Lung Transplant Ischemia–Reperfusion Injury
Emphysema-associated Autoreactive Antibodies Exacerbate Post–Lung Transplant Ischemia–Reperfusion Injury
- Source :
- American Journal of Respiratory Cell and Molecular Biology. 60:678-686
- Publication Year :
- 2019
- Publisher :
- American Thoracic Society, 2019.
-
Abstract
- Chronic obstructive pulmonary disease-associated chronic inflammation has been shown to lead to an autoimmune phenotype characterized in part by the presence of lung autoreactive antibodies. We hypothesized that ischemia-reperfusion injury (IRI) liberates epitopes that would facilitate preexisting autoantibody binding, thereby exacerbating lung injury after transplant. We induced emphysema in C57BL/6 mice through 6 months of cigarette smoke (CS) exposure. Mice with CS exposure had significantly elevated serum autoantibodies compared with non-smoke-exposed age-matched (NS) mice. To determine the impact of a full preexisting autoantibody repertoire on IRI, we transplanted BALB/c donor lungs into NS or CS recipients and analyzed grafts 48 hours after transplant. CS recipients had significantly increased lung injury and immune cell infiltration after transplant. Immunofluorescence staining revealed increased IgM, IgG, and C3d deposition in CS recipients. To exclude confounding alloreactivity and confirm the role of preexisting autoantibodies in IRI, syngeneic Rag1-/- (recombination-activating protein 1-knockout) transplants were performed in which recipients were reconstituted with pooled serum from CS or NS mice. Serum from CS-exposed mice significantly increased IRI compared with control mice, with trends in antibody and C3d deposition similar to those seen in allografts. These data demonstrate that pretransplant CS exposure is associated with increased IgM/IgG autoantibodies, which, upon transplant, bind to the donor lung, activate complement, and exacerbate post-transplant IRI.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
Clinical Biochemistry
Ischemia
Inflammation
Lung injury
Epitope
03 medical and health sciences
0302 clinical medicine
medicine
Molecular Biology
Lung
biology
business.industry
Autoantibody
Cell Biology
medicine.disease
030104 developmental biology
medicine.anatomical_structure
030228 respiratory system
Immunology
biology.protein
Antibody
medicine.symptom
business
Reperfusion injury
Subjects
Details
- ISSN :
- 15354989 and 10441549
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory Cell and Molecular Biology
- Accession number :
- edsair.doi...........2e0f164af37cd9544a320fee9016b202
- Full Text :
- https://doi.org/10.1165/rcmb.2018-0224oc