IMMUNOHISTOCHEMICAL EVIDENCE FOR LOSS OF ICAM-1 BY ALVEOLAR EPITHELIAL-CELLS IN PULMONARY FIBROSIS

ICAM-1 is an intercellular adhesion molecule of the immunoglobulin sup ergene family involved in adherence of leukocytes to the endothelium a nd in leukocytic accumulation in pulmonary injury. In the current stud y, the antigen retrieval technique was used to detect ICAM-1 immunohis tochemically in paraffin sections of lungs from human, mouse and rat a s well as in bleomycin- or radiation-induced fibrotic lungs from rat a nd human. In normal lung tissue, the expression of ICAM-1 on alveolar type I epithelial cells is stronger than on alveolar macrophages and o n endothelial cells. Preembedding immunoelectron microscopy of normal rat, mouse and human lung samples revealed selective ICAM-1 expression on the surface of type I alveolar epithelial cells and, to a lesser e xtent, on the pulmonary capillary endothelium and on alveolar macropha ges. In fibrotic specimens, both focal lack and strengthening of immun ostaining on the surface of type I cells was found. Alveolar macrophag es were found focally lacking ICAM-1 immunoreactivity. In some cases, rat type II pneumocytes exhibited positive immunoreactions for ICAM-1. Immunoelectron microscopy with preembedded rat lungs (bleomycin-expos ed cases) confirmed the altered ICAM-1 distribution at the alveolar ep ithelial surface. In the alveolar fluid of fibrotic rat lungs, in cont rast to that from untreated controls, soluble ICAM-1 was detected by w estern blot analysis.