Am. J. Respir. Cell Mol. Biol., Volume 19, Number 4, October, 1998 598-605

Glucocorticoid-Induced Apoptosis of Dendritic Cells in the Rat Tracheal Mucosa

James J. Brokaw, Gary W. White, Peter Baluk, Gary P. Anderson, Eric Y. Umemoto, and Donald M. McDonald

Department of Anatomy, Indiana University School of Medicine, Evansville, Indiana; Cardiovascular Research Institute and Department of Anatomy, University of California, San Francisco, California; and Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia

Dendritic cells are antigen-presenting cells that constitutively express high levels of major histocompatibility complex class II (Ia) antigen on their plasma membrane. Previous studies have shown that the number of dendritic cells in the rat airway mucosa decreases rapidly after glucocorticoid treatment. We sought to determine whether apoptosis contributes to this steroid-induced cell decrease. Dendritic cells in tracheal whole mounts were revealed by immunoperoxidase staining using the OX-6 (anti-Ia) monoclonal antibody. In untreated rats, a dense network of Ia-immunoreactive (Ia⁺) cells with highly branched cytoplasmic processes was observed just beneath the tracheal epithelium (1,405 ± 140 cells/mm² mucosa; mean ± SEM, n = 6). In rats treated with dexamethasone (10 mg/kg, intraperitoneally), four distinct changes in dendritic cell morphology were evident 4 to 8 h after injection: (1) appearance of large Ia⁺ granules in cytoplasmic processes, (2) narrowing of cytoplasmic processes, (3) loss of Ia immunoreactivity from the cell surface, and (4) fragmentation of cells into small Ia⁺ bodies. These changes accompanied a 56% decrease in the number of Ia⁺ cells over 8 h. The contribution of apoptosis to this decrease in Ia⁺ cells was determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) of nucleosomal DNA fragments in histologic sections. The number of TUNEL⁺ bodies increased from a control value of 174 ± 47 bodies/mm² mucosa to 2,108 ± 294 bodies/mm² mucosa at 4 h and 936 ± 343 bodies/ mm² mucosa at 8 h (n = 4 rats per time point). The location of TUNEL⁺ bodies closely corresponded to that of Ia⁺ cells stained in adjacent histologic sections. We conclude that apoptosis contributes to the rapid decrease in airway dendritic cells after glucocorticoid treatment.

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