Human monocytes released superoxide anion, prostaglandin E2, leukotriene B4, IL-1, and TNF when exposed t plastic surfaces coated with murine anti-CD3 monoclonal antibody, OKT3. Stimulation of mediator release by OKT3 was dependent on the amount of antibody immobilized onto wells of plastic tissue culture plates. Soluble antibody or antibody adsorbed to moncytes and reacted with an aggregating (""""""""cross-linking"""""""") second antibody failed to induce mediator release. Monocytes """"""""armed"""""""" with OKT3 formed rosettes with T cells in a fashion indistinguishable from that seen between monocytes and sensitized T cells. Monocytes with adsorbed OKT3 antibodies released IL-1B and TNF-a when exposed to unsensitized T cells, although increased superoxide release could not be detected. OKT4a, a murine IgG2a antibody which reacts with a different T cell epitope (CD4), failed to induce cytokine the presence of IL-2 or IFN-y. These data indicate that certain antibodies bound to Fc receptors of monocytes may trigger monocyte function when reacting with cells bearing the appropriate target antigens. FcR-mediated signalling resulting in mediator release may be involved in initiating or regulating the immune response. Furthermore, systemically a administered monoclonal antibodies may induce inflammatory responses and their attendant symptomatologies via their interaction with FcR-bearing inflammatory cells.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BH002019-02
Application #
3792635
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Center Biologics Evaluation Research Hematology
Department
Type
DUNS #
City
State
Country
United States
Zip Code