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

Abstract

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.

Anatomical Location Determines the Distribution and Function of Dendritic Cells and Other APCs in the Respiratory Tract

“…8). This may represent a potential mechanism for rapid local tissue memory T cell activation by pathogen-derived peptides released by local phagocytes, which our group and others have shown to be recruited into the airway mucosa during acute inflammatory responses (30), while restricting naive T cell activation to whole protein Ags to DLNs.…”

Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells

“…Besides the previously reported negative effects on DC trafficking (34), function (25,30) and increases in apoptosis of DC (35), glucocorticoids also have shown in many studies variable`suppressive' and`altering' effects on the maturation of DC. This probably depends on the dose and time schedule of exposure, and the maturation state of the target DC population.…”

Improved survival ratios correlate with myeloid dendritic cell restoration in acute-on-chronic liver failure patients receiving methylprednisolone therapy

“…These data are in agreement with previous studies that showed that glucocorticoid can induce the apoptosis of DCs. 21 The sequential responses were uniquely found in survivors but not in NS patients because mDC recovery occurred drastically and almost simultaneously with improved liver function. Although our data suggest that a strong mDC recovery may be an important factor for favorable responses to MP treatment, it was rational to speculate that the rebound of circulating mDC numbers may not simply be a direction result of the redistribution of mDCs from the liver, where they function as effectors of ACLF pathogenesis, to the blood.…”