Article

Ultrastructural changes in acute lung allograft rejection: novel insights from an animal study.

Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation (Impact Factor: 3.54). 01/2012; 31(1):94-100. DOI: 10.1016/j.healun.2011.10.003
Source: PubMed

ABSTRACT Acute rejection (AR) episodes after lung transplantation (Tx) are orchestrated by cells of the innate and adaptive immune system targeting the engrafted organ. The assessment and classification of pathologic changes of AR relies essentially on conventional histology. Herein we apply the technique of scanning electron microscopy (SEM) to identify and characterize ultrastructural changes of the pulmonary graft after lung Tx.
Orthotopic single-lung Tx was performed between BALB/c (donor) and C57BL/6 (recipient) mice. At Day 5 after Tx, lung allografts were recovered for SEM and for histologic analysis.
Upon Tx, high numbers of leukocytes and thrombocytes were found, showing an activated surface pattern and a change of their cell body shape. These cells adhered and partly transmigrated through the endothelium of vessels. Larger vessels were more affected than smaller vessels and the endothelium was roughened in its surface texture throughout. As a phenomenon, airways were partly covered by activated dendritic cells. Numerous thrombocytes and macrophages accumulated on the endothelium of the cuff anastomosis region exposing this area to a particularly higher risk of thrombosis.
SEM allows for detection of morphologic changes during pulmonary allograft rejection and adds important data to conventional histology when making the diagnosis of acute rejection.

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    ABSTRACT: It has been 5 years since our team reported the first successful model of orthotopic single lung transplantation in the mouse. There has been great demand for this technique due to the obvious experimental advantages the mouse offers over other large and small animal models of lung transplantation. These include the availability of mouse-specific reagents as well as knockout and transgenic technology. Our laboratory has utilized this mouse model to study both immunological and non-immunological mechanisms of lung transplant physiology while others have focused on models of chronic rejection. It is surprising that despite our initial publication in 2007 only few other laboratories have published data using this model. This is likely due to the technical complexity of the surgical technique and perioperative complications, which can limit recipient survival. As two of the authors (XL and WL) have a combined experience of over 2500 left and right single lung transplants, this review will summarize their experience and delineate tips and tricks necessary for successful transplantation. We will also describe technical advances made since the original description of the model.
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May 31, 2014