Glucocorticoid-mediated generation of suppressor macrophages with high density FcγRII during acute cold stress

Abstract

Acute cold stress induces adherent cells with suppresser function, resulting in immunosuppression. Glucocorticoids (GC) are known as an inhibitor of the immune system and are increased by stress through stimulation of the hypothalamic-pituitary-adrenal axis. To elucidate the mechanisms underlying acute cold stress-induced immunosuppression, functions and surface phenotypes of murine peritoneal cells of the monocyte/macrophage lineage from acute cold-stressed mice (5 C for 3 or 24 h) in addition to the role of GC in the immunomodulation were investigated. Flow cytometric analysis revealed that the proportion of MAC-1+ cells with a high density of FcγRII (FcγRII(bright) cells) was markedly increased in the peritoneal exudate cells from acute cold-stressed mice. These FcγRII(bright) cells were also stained with F4/80, a monoclonal antibody directed specifically against the mouse mature macrophages. The prominent suppressor activity for Concanavalin A (Con A) responses of control spleen cells was found in FcγRII(bright) cells, whereas MAC-1+ cells, with a low density of FcγRII (FcγRII(dull) cells), from the stressed mice did not suppress the Con A responses. FcγRII(bright) cells from control mice also suppressed the Con A responses; the inhibitory effect was considerably less than that of cells from acute cold-stressed mice. As was anticipated, serum corticosterone levels were markedly increased in acute cold-stressed mice. In addition, expression of GC receptor messenger RNA was observed in FcγRII(bright) cells from these mice. The increase in FcγRII(bright) cells in peritoneal exudate cells caused by acute cold stress was inhibited by adrenalectomy or administration of a saturating amount of the GC antagonist RU 38486 (mifepristone). On the contrary, administration or the Gc agonist, dexamethasone, markedly increased the proportion of FcγRII(bright) cells in peritoneal exudate cells of control mice. These results suggest that the generation of FcγRII(bright) suppresser cells of monocyte/macrophage lineage by acute cold stress was mediated to a greater or lesser degree by the action of GC through the GC receptor.