title: Mechanism of human monocyte activation via the 40-kDa Fc receptor for IgG.
abstract: It is shown that a mAb specific for the human 40-kDa FcR (FcRII) leads to activation of human monocytic cells but that extensive cross-linking of the receptor is required. Calcium mobilization can be induced in immature monocytic cells (undifferentiated U937 cells) and peripheral blood monocytes with an intact IgG1 anti-FcRII antibody (CIKM5) but not by F(ab')2 fragments of this antibody. The intact antibody can bind in a tripartite manner by its two F(ab') sites and its Fc-binding site whereas the F(ab')2 fragments of this antibody can only bind in a divalent fashion. A rise in intracellular free calcium ion concentration occurs when F(ab')2 fragments are cross-linked with F(ab')2 anti-mouse Ig indicating that more extensive cross-linking of FcRII is required rather than an obligatory requirement for an Fc-FcRII interaction. Calcium mobilization in response to intact or cross-linked F(ab')2 fragments of CIKM5 is associated with superoxide production only in IFN-gamma-primed peripheral blood monocytes and IFN-gamma differentiated U937 cells indicating that the activation signal produced via FcRII is inadequate to fully stimulate non-"primed" cells. A second mAb reactive with FcRII (2E1) does not cause calcium mobilization in monocytes or U937 cells, and partially blocks the effects of CIKM5. 2E1 also blocks CIKM5 superoxide production in IFN-gamma-primed monocytes and differentiated U937 cells. This may be explained in part by the fact that 2E1 is an IgG2a antibody and can only participate in bipartite binding with FcRII. When 2E1 is cross-linked with F(ab')2 anti-mouse Ig there is a small calcium response. This does not cause superoxide generation in IFN-primed monocytes but does do so in IFN-gamma differentiated U937 cells. FcRII is also expressed on granulocytes and some B cells but the effects of cross-linking the receptor on these cells differ from those seen in monocytes.
authors.affiliation: Department of Haematology, Middlesex Hospital, London, England.
authors.forename: E A
authors.initials: EA
authors.lastname: MacIntyre
authors.forename: P J
authors.initials: PJ
authors.lastname: Roberts
authors.forename: R
authors.initials: R
authors.lastname: Abdul-Gaffar
authors.forename: K
authors.initials: K
authors.lastname: O'Flynn
authors.forename: G R
authors.initials: GR
authors.lastname: Pilkington
authors.forename: F
authors.initials: F
authors.lastname: Farace
authors.forename: J
authors.initials: J
authors.lastname: Morgan
authors.forename: D C
authors.initials: DC
authors.lastname: Linch
mesh_terms: D000911:Antibodies, Monoclonal / Q000502:physiology; D000943:Antigens, Differentiation / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003429:Cross Reactions; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D007074:Immunoglobulin G / Q000378:metabolism*; D008262:Macrophage Activation; D008970:Molecular Weight; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D011961:Receptors, Fc / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D017452:Receptors, IgG; D013481:Superoxides / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D013481:Superoxides; D002118:Calcium