ABSTRACT
We report the case of a 52-year-old female, who received a left single lung transplantation for end-stage smoking-induced emphysema in 1997. During the last 4 years, she experienced a progressive decline in FEV1, which we attributed to the development of bronchiolitis obliterans syndrome, stage 2. In 2007 she experienced an invasive aspergillosis of the native lung upper lobe, which resolved after 3 months of adequate treatment with voriconazole. After resolution of the infection, both FVC (forced vital capacity) and FEV1 became surprisingly better, due to fibrosis of the affected lobe, compatible with infection-induced volume reduction of the native lung.
Subject(s)
Emphysema/surgery , Invasive Pulmonary Aspergillosis/complications , Lung Transplantation , Pulmonary Fibrosis/microbiology , Pulmonary Fibrosis/physiopathology , Female , Forced Expiratory Volume , Humans , Invasive Pulmonary Aspergillosis/pathology , Middle Aged , Pulmonary Fibrosis/pathology , Vital CapacityABSTRACT
Ischaemia-reperfusion injury of the lung is a major cause of morbidity and mortality, particularly following lung transplantation, the mainstay treatment for patients with end-stage pulmonary disease. Effective measures to prevent this complication are lacking. Thrombomodulin (TM) is an endothelial cell receptor and cofactor for thrombin-mediated generation of the anticoagulant and anti-inflammatory activated protein C (APC). The N-terminal lectin-like domain (LLD) of TM has no direct effects on coagulation, but has distinct anti-inflammatory properties, interfering with leukocyte adhesion, complement activation and cytokine generation, all of which are hallmarks of ischaemia-reperfusion injury. Using a murine model of lung ischaemia-reperfusion injury (90 min ischaemia, 4 h reperfusion), the present study shows that mice lacking the LLD of TM respond with increased extravasation of neutrophils and macrophages into the lung parenchyma and bronchoalveolar fluid (BALF), with augmented BALF levels of cytokines interleukin (IL)-1beta and granulocyte-monocytic colony-stimulating factor (GM-CSF). Pre-treatment of wild-type mice with recombinant LLD, as compared with controls, significantly suppresses protein leakage and accumulation of leukocytes in the BALF. These novel findings support further evaluation of recombinant lectin-like domain of thrombomodulin to protect the lung against tissue-damaging pro-inflammatory responses following ischaemia-reperfusion.
Subject(s)
Lectins/chemistry , Lung Injury/pathology , Reperfusion Injury/metabolism , Thrombomodulin/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anticoagulants/chemistry , Blood Coagulation , Bronchoalveolar Lavage Fluid , Endothelial Cells/metabolism , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Lung Injury/mortality , Mice , Models, Biological , Protein C/chemistry , Protein Structure, Tertiary , Reperfusion Injury/prevention & controlABSTRACT
In a murine model of lung ischemia-reperfusion injury (IRI), we previously demonstrated that lymphocytes increase in the alveolar space during the ischemic period. We hypothesized that these lymphocytes play an important role during ischemia in the development of lung IRI. In the present study, severe combined immunodeficiency (SCID) mice, lacking T cells, were used to further investigate our hypothesis. SCID and control mice underwent 90 minutes of left lung ischemia followed by 4 hours of reperfusion. A significant decrease in neutrophils, together with lower levels of interleukin-1beta, was found in SCID mice after reperfusion. We concluded that lymphocytes invading the lung during ischemia trigger an inflammatory response upon reperfusion. Antilymphocyte therapies in the donor should be further investigated as treatment strategies against IRI.
