Influence of suramin on the expression of Fc receptors and other markers on human monocytes and U937 cells, and on their phagocytic properties.
Suramin, a polyanionic and polycyclic compound, was initially used for the treatment of trypanosomiasis and onchocerciasis. In the last decade, it has been used in therapy of cancer and acquired immune deficiency syndrome (AIDS). The influence of suramin on the expression of various markers by human mononuclear phagocytes is not known and was, therefore, presently investigated. Suramin inhibited the proliferation of U937 cells and mitogen-induced T-cell proliferation in a dose-dependent manner. The constitutive and cytokine-driven expression of Fc receptors for IgG (Fc gamma RI and Fc gamma RII), IgE (Fc epsilon RII) and IgA (Fc alpha R) on blood monocytes and U937 cells was suppressed by suramin. The basal level, as well as cytokine-induced major histocompatibility complex (MHC) class II antigens, was markedly diminished on suramin-treated monocytes. Furthermore, suramin dramatically reduced expression of CD14 and partially reduced complement receptor type 3 (CR3) and CR4 expression on monocytes. In contrast, suramin slightly induced MHC class I antigens on monocytes and CD71 on U937 cells. The capacity of monocytes to phagocytose IgG-sensitized ox erythrocytes, opsonized Escherichia coli, or fluorescein isothiocyanate (FITC)-conjugated latex beads was significantly inhibited. Northern blot analysis showed that the amount of Fc epsilon RII-specific mRNA was only partially reduced, suggesting that other mechanisms may be involved in the regulation of Fc epsilon RII expression. Our data demonstrate that suramin suppresses the expression of various cell-surface structures on human mononuclear phagocytes and impairs their phagocytic capacity.
Institute of General and Experimental Pathology, University of Vienna, Austria.
C
C
Schiller
A
A
Spittler
M
M
Willheim
Z
Z
Szépfalusi
H
H
Agis
M
M
Köller
M
M
Peterlik
G
G
Boltz-Nitulescu
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006680:HLA Antigens / Q000187:drug effects; D006801:Humans; D009000:Monocytes / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects; D011951:Receptors, Complement / Q000187:drug effects; D011961:Receptors, Fc / Q000187:drug effects*; D017455:Receptors, IgE / Q000235:genetics; D013498:Suramin / Q000494:pharmacology*
D006680:HLA Antigens; D012333:RNA, Messenger; D011951:Receptors, Complement; D011961:Receptors, Fc; D017455:Receptors, IgE; D013498:Suramin