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

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.