GLUCOCORTICOID-MEDIATED GENERATION OF SUPPRESSOR MACROPHAGES WITH HIGH-DENSITY FC-GAMMA-RII DURING ACUTE COLD STRESS

Acute cold stress induces adherent cells with suppressor function, res ulting in immunosuppression. Glucocorticoids (GC) are known as an inhi bitor of the immune system and are increased by stress through stimula tion of the hypothalamic-pituitary-adrenal axis. To elucidate the mech anisms underlying acute cold stress-induced immunosuppression, functio ns and surface phenotypes of murine peritoneal cells of the monocyte/m acrophage 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(+) cel ls with a high density of Fc gamma RII (Fc gamma RII(bright) cells) wa s markedly increased in the peritoneal exudate cells from acute cold-s tressed mice. These Fc gamma RII(bright) cells were also stained with F4/80, a monoclonal antibody directed specifically against the mouse m ature macrophages. The prominent suppressor activity for Concanavalin A (Con A) responses of control spleen cells was found in Fc gamma RII( bright) cells, whereas MAC-1(+) cells, with a low density of Fc gamma RII (Fc gamma RII(bright) cells), from the stressed mice did not suppr ess the Con A responses. Fc gamma RII(bright) cells from control mice also suppressed the Con A responses; the inhibitory effect was conside rably less than that of cells from acute cold-stressed mice. As was an ticipated, serum corticosterone levels were markedly increased in acut e cold-stressed mice. In addition, expression of GC receptor messenger RNA was observed in Fc gamma RII(bright) cells from these mice. The i ncrease in Fc gamma RII(bright) cells in peritoneal exudate cells caus ed by acute cold stress was inhibited by adrenalectomy or administrati on of a saturating amount of th GC antagonist RU 38486 (mifepristone). On the contrary, administration of the GC agonist. dexamethasone, mar kedly increased the proportion of Fc gamma RII(bright) cells in perito neal exudate cells of control mice. These results suggest that the gen eration of Fc gamma RII(bright) suppressor cells of monocyte/macrophag e lineage by acute cold stress was mediated to a greater or lesser deg ree by the action of GC through the GC receptor.