COEXPRESSION OF ASPARTIC PROTEINASES AND HUMAN-LEUKOCYTE ANTIGEN-DR IN HUMAN TRANSPLANTED LUNG

Aspartic proteinases have recently been shown to be implicated in anti gen processing. We explored the expression of two aspartic proteinases , cathepsins B and D, and of human leukocyte antigen-DR (NLA-DR) molec ules in a consecutive series of 80 transbronchial biopsies from transp lanted lungs. For controls, we studied five normal donor lungs (not su itable for transplantation on account of thoracic trauma) and macrosco pically normal areas of three cancer-affected lungs. Two of the five u nsuitable donor lungs showed minimal inflammatory changes. Macroscopic ally normal samples from the three cancerous lungs showed mild and foc al inflammatory infiltrates, In histologically normal lungs, HLA-DR ex pression was limited to professional antigen-presenting cells. Macrosc opically normal lung samples with minimal inflammatory changes from bo th donor and cancer lungs showed variable HLA-DR expression by alveola r and bronchial epithelial cells and by endothelial cells. All transpl anted lung biopsies showed HLA-DR expression by epithelial (alveolar a nd bronchial) and endothelial cells, with a trend for increased positi vity in acute rejection. Cathepsin E was restricted to Clara and to ra re bronchus-associated lymphoid tissue-related epithelial cells in his tologically normal lung samples, whereas minimal de novo cathepsin E e xpression by rare alveolar pneumocytes was noted in control lung sampl es exhibiting minimal inflammatory changes. In all transplanted lung b iopsies, cathepsin E was diffusely expressed de novo by hyperplastic a lveolar epithelial cells, regardless of the presence or degree of reje ction, Cathepsin D was expressed only by alveolar macrophages and by c iliated bronchial cells of normal, minimally inflamed and transplanted lungs. In transplanted lung, Clara cells and several hyperplastic alv eolar pneumocytes coexpressed HLA-DR and cathepsin E, whereas all alve olar macrophages and a few ciliated cells coexpressed cathepsin D and HLA-DR The present investigation suggests that the de novo expression of cathepsin E and HLA-DR by hyperplastic alveolar pneumocytes of tran splanted lung may be crucial for antigen processing and presentation t o recipient competent T cells, and thus for the triggering of the immu ne-inflammatory cascade that leads to rejection.