Stimulation of human monocytes by anti-CD3 monoclonal antibody: induction of inflammatory mediator release via immobilization of Fc receptor by adsorbed immunoglobulin and T-lymphocytes.
Human monocytes released superoxide anion, prostaglandin E2, leukotriene B4, IL-1, and TNF when exposed to plastic surfaces coated with murine anti-CD3 monoclonal antibody, OKT 3. Stimulation of mediator release by OKT 3 was dependent on the amount of antibody immobilized onto wells of plastic tissue culture plates. Soluble antibody or antibody adsorbed to monocytes and reacted with an aggregating ("cross-linking") second antibody failed to induce mediator release. Monocytes "armed" with OKT 3 formed rosettes with T cells in a fashion indistinguishable from that seen between monocytes and T cells sensitized with OKT 3. Monocytes with adsorbed OKT 3 antibodies released IL-1 beta and TNF-alpha when exposed to unsensitized T cells, although increased superoxide release could not be detected. OKT 4a, a murine IgG2a antibody that reacts with a different T cell epitope (CD4), failed to induce cytokine release from monocytes when cross-linked by T cells or a CD4+ T cell line, even in the presence of IL-2 or IFN-gamma. These data indicate that certain antibodies bound to Fc receptors (FcR) of monocytes may trigger monocyte function when reacting with cells bearing the appropriate target antigens. FcR-mediated signaling resulting in mediator release may be involved in initiating or regulating the immune response. Furthermore, systemically administered monoclonal antibodies may induce inflammatory responses and their attendant symptomatologies via their interaction with FcR-bearing inflammatory cells.
Hoffman
T
T
Laboratory of Cell Biology, U.S. Food and Drug Administration, Bethesda, Maryland 20892.
Tripathi
A K
AK
Lee
Y L
YL
Lizzio
E F
EF
Bonvini
E
E
D000327:Adsorption; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D015232:Dinoprostone / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D007375:Interleukin-1 / Q000097:blood; D007975:Leukotriene B4 / Q000097:blood; D009000:Monocytes / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*; D012397:Rosette Formation; D013481:Superoxides / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007074:Immunoglobulin G; D007375:Interleukin-1; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D007975:Leukotriene B4; D015232:Dinoprostone