title: Effect of N-acetylcysteine on acute allograft rejection after rat lung transplantation.
abstract: 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.
authors: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland. barbara.erne@gmx.at
authors: Barbara V
authors: BV
authors: Erne
authors: Wolfgang
authors: W
authors: Jungraithmayr
authors: Johanna
authors: J
authors: Buschmann
authors: Stephan
authors: S
authors: Arni
authors: Walter
authors: W
authors: Weder
authors: Ilhan
authors: I
authors: Inci
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D007113:Immunity, Innate / Q000187:drug effects*; D007150:Immunohistochemistry; D016040:Lung Transplantation; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D051116:Receptors, Scavenger; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D000111:Acetylcysteine; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016166:Free Radical Scavengers; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D000098902:CD163 Antigen; C539355:CD68 protein, rat; D000097382:CD68 Molecule