Effect of N -Acetylcysteine on Acute Allograft Rejection After Rat Lung Transplantation

• Published in: The Annals of thoracic surgery Vol. 95; no. 3; pp. 1021 - 1027
• Main Authors: Erne, Barbara V., MD, Jungraithmayr, Wolfgang, MD, PhD, Buschmann, Johanna, PhD, Arni, Stephan, PhD, Weder, Walter, MD, Inci, Ilhan, MD
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.03.2013
• Subjects: Acetylcysteine - pharmacology; Acute Disease; Animals; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - immunology; Antigens, Differentiation, Myelomonocytic - metabolism; Cardiothoracic Surgery; Disease Models, Animal; Free Radical Scavengers - pharmacology; Graft Rejection - etiology; Graft Rejection - immunology; Graft Rejection - prevention & control; Immunity, Innate - drug effects; Immunohistochemistry; Lung Transplantation; Macrophages, Alveolar - immunology; Macrophages, Alveolar - metabolism; Male; Rats; Rats, Inbred BN; Rats, Inbred Lew; Receptors, Cell Surface - immunology; Receptors, Cell Surface - metabolism; Receptors, Scavenger; Reperfusion Injury - complications; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology; Surgery; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transplantation, Homologous; 12
• ISSN: 0003-4975; 1552-6259
• DOI: 10.1016/j.athoracsur.2012.11.008

Background N -Acetylcysteine (NAC) attenuates ischemia–reperfusion injury after lung transplantation in animal models. The purpose of this study is to evaluate a protective effect of NAC against acute lung rejection. Methods Rat single-lung transplantation was performed in four groups (n = 7 per group). In NAC groups, donors and recipients received NAC 150 mg/kg per day intraperitoneally before transplantation and recipients thereafter until euthanasia. Control groups (CON) received 0.5 mL of 0.9% saline solution intraperitoneally instead of NAC. Animals were euthanized on day 1 (CON1, NAC1) or day 5 (CON5, NAC5) after transplantation. Lung tissue was assessed by histology, immunohistochemistry for CD68+/CD163+ macrophages and CD3+ T cells, immunofluorescence for interleukin 4 and interleukin 12, concentration of reduced glutathione, and activated nuclear factor-kappa B. Results CD68+ macrophages in CON5 accumulated significantly compared with NAC5 grafts ( p < 0.001). No significant difference was observed for CD163+ macrophages on day 5. T cells were significantly more frequent in NAC1 ( p < 0.001), but significantly less in NAC5 ( p < 0.001) compared with control groups, respectively. Interleukin 4 and interleukin 12 expression did not differ between groups. Treatment with NAC significantly influenced glutathione levels ( p = 0.019) and reduced nuclear factor-kappa B activation ( p = 0.034) in transplanted lungs. Conclusions N -Acetylcysteine has the potential to attenuate acute pulmonary rejection by reduction of macrophage and T-cell infiltration, which is intimately linked to a reduced action of the nuclear factor-kappa B proinflammatory signaling pathway. In view of these observations, NAC should be considered a promising substance that could play a role in strategies for the prevention of acute rejection.