In vivo glucocorticoid modulation of guinea pig splenic macrophage Fc gamma receptors.

Abstract

Although glucocorticoids are widely used in the treatment of immunohematologic disease, their relative efficacy is uncertain. We used an animal model, which has helped to elucidate the role of splenic macrophage Fc'y receptors in the clearance of IgG-coated cells, to investigate whether each Fc'y receptor is modulated by glucocorticoids to the same extent and to examine the relative potency of three commonly used glucocorticoids. Cortisol, prednisone, and dexamethasone all impaired the clearance ofIgG-coated erythrocytes. However, dexamethasone was more effective than either prednisone or cortisol (P < 0.001). Furthermore, splenic macrophages isolated from glucocorticoid-treated animals expressed impaired Fcy receptor function. This effect was greater in macrophages isolated from dexamethasone-treated animals, as compared to either cortisol-or prednisone-treated animals (P < 0.001). To assess the effect of glucocorticoids on the two types of guinea pig splenic macrophage Fc-y receptors, FcyR1,2 and FcyR2, specific immunoglobulin isotypes were used to measure macrophage binding of IgG-sensitized erythrocytes. Cortisol and prednisone primarily affected FcyR2, whereas dexamethasone inhibited the function of both guinea pig Fcy receptors. Furthermore, dexamethasone was more effective (P < 0.01) than either prednisone or cortisol in inhibiting the ability of both receptors to bind IgG-sensitized cells. Fluorescence-activated cell sorter analysis and fluorescence microscopy with monoclonal antibodies specific for each of these two receptors demonstrated that essentially all splenic macrophages expressed both receptors, and that these glucocorticoids decreased the level of each Fcy receptor protein expressed, rather than altering receptor mobility and clustering in the macrophage membrane. The effect on both Fcy receptors was greatest with dexamethasone and least with cortisol. These studies demonstrate the significant role of guinea pig splenic macrophage (J. Clin. Invest. 1991. 88:149-157.)

Enhancement of Splenic-Macrophage Fcγ Receptor Expression by Treatment with Estrogens

“…Guinea pigs were injected with equal volumes of a homogeneous suspension of estrogens in steroid suspension vehicle (SSV) (8,15). Sham controls received 1 ml of SSV not containing estrogen.…”

“…Chlortianisene (Ct) and promestriene (Pm) were obtained from the pharmacy of our hospital. Doses of estrogens were selected on the basis of those previously used in the treatment of human conditions: 0.005 to 1 mg/kg of body weight for Et, 0.5 to 10 mg/kg for M, 0.5 to 10 mg/kg for Ct, 0.1 to 5 mg/kg for Pm, 2.5 to 10 mg/kg for Ep, and 2.5 to 10 mg/kg for E. Rabbit IgG anti-guinea pig red blood cell (RBC) antibodies were prepared as previously described, purified by Sephacryl S-300 gel filtration and quaternary aminoethyl ion-exchange chromatography (Pharmacia, Piscataway, N.J.), and free of IgM as determined by Ouchterlony analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (7,8,15).…”

“…Blood was drawn from anesthetized guinea pigs by cardiac puncture. Washed erythrocytes were radiolabeled with [ 51 Cr]sodium chromate (Amersham, Madrid, Spain) and sensitized with an equal volume of IgG antibody, so as to be coated with approximately 3,500 IgG molecules per erythrocyte as described previously (8,15). Treated animals were injected intravenously with 1.7 ϫ 10 8 51 Cr-labeled cells.…”

“…We have studied the effects of the treatment with estrogens approved for clinical use upon splenic-macrophage Fc␥R expression using a well-characterized experimental model, the guinea pig (7,8,15).…”

Cyclophosphamide Exerts No Beneficial Effect over Prednisone Alone in the Initial Treatment of Acute Immune-Mediated Hemolytic Anemia in Dogs: A Randomized Controlled Clinical Trial

“…Prednisone therapy also may reduce the numbers of erythrocyte-bound and unbound antibodies during chronic management of this disease. 9 Human IMHA patients who fail to respond to steroid therapy alone within 4-6 weeks often receive additional immunosuppressive agents in combination with prednisone to achieve greater immunosuppression. These agents in-clude cyclophosphamide, azathioprine, danazol, cyclosporine, and human IV IgG.…”