title: Modulation of human mononuclear phagocyte Fc gamma RII mRNA and protein.
abstract: Human monocytes and macrophages express three different classes of cell surface receptors for the Fc portion of IgG, Fc gamma RI (CD64), Gc gamma RII (CD32), and Fc gamma RIII (CD16). We utilized a cDNA probe for Fc gamma RII to examine the modulation of Fc gamma RII mRNA by dexamethasone, a synthetic glucocorticoid, and interferon-gamma. We also determined the changes in the expression of both Fc gamma RI and Fc gamma RII protein following treatment with these agents by flow cytometry. In studies performed with the monocyte-like cell line. U937, Northern blot analysis revealed that cells treated with interferon-gamma showed a 2.5-fold increase in Fc gamma RII mRNA levels that was maximal at 14 hr and declined to 1.4-fold over baseline by 48 hr of incubation. Treatment of U937 cells with dexamethasone did not significantly change the level of Fc gamma RII transcripts, but was able to inhibit by up to 50% the increase seen following interferon-gamma treatment. The expression of Fc gamma RII protein on U937 cells was increased 56-72% after 16-24 hr of interferon-gamma treatment, but was only 18% over baseline after 48 hr of incubation. Treatment with dexamethasone caused a small, but significant, decrease in Fc gamma RII protein, and inhibited by 20-60% the induction of Fc gamma RII by interferon-gamma. The modulation by dexamethasone and interferon-gamma of Fc gamma RI protein expression on U937 cells was markedly different from that of Fc gamma RII in both magnitude and kinetics. Interferon-gamma treatment increased Fc gamma RI expression by 240% at 16 hr, and Fc gamma RI remained elevated through 48 hr. Treatment with dexamethasone decreased Fc gamma RI expression by 39%, and also inhibited by 40% the increase induced by interferon-gamma. In contrast to the findings with U937 cells, dexamethasone and/or interferon-gamma treatment had no significant effect on Fc gamma RII mRNA levels or protein expression in monocytes. However, interferon-gamma treatment increased Fc gamma RI expression on monocytes, and this increase was further augmented by treatment with dexamethasone. These data indicate that the modulation of Fc gamma RII on U937 cells is at least in part due to changes in steady state levels of Fc gamma RII mRNA. The difference between the magnitude of the changes in Fc gamma RII mRNA and protein suggests that some translational or post-translational control is involved in regulating the expression of Fc gamma RII.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: P G
authors.initials: PG
authors.lastname: Comber
authors.forename: M D
authors.initials: MD
authors.lastname: Rossman
authors.forename: E F
authors.initials: EF
authors.lastname: Rappaport
authors.forename: P
authors.initials: P
authors.lastname: Chien
authors.forename: P M
authors.initials: PM
authors.lastname: Hogarth
authors.forename: A D
authors.initials: AD
authors.lastname: Schreiber
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D015342:DNA Probes; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism; D017452:Receptors, IgG; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015342:DNA Probes; D012333:RNA, Messenger; D011961:Receptors, Fc; D017452:Receptors, IgG; D003907:Dexamethasone; D007371:Interferon-gamma