Inflammatory mediator release from human monocytes via immobilized Fc receptors. Its potential role in adverse reactions to systemic monoclonal antibody therapy.
Human monocytes released superoxide anion, IL-1, and TNF subsequent to binding of their Fc receptor I to murine IgG2a or rabbit IgG. Fc receptor II binding to murine IgG2b or IgG1 had similar consequences. Immobilized murine monoclonal antibodies, IgG2a anti-CD3 (OKT3) or IgG1 anti-CD44 also induced superoxide anion and monokine production. Monocytes bound OKT3 via FcRI and responded to immobilized OKT3 by inflammatory mediator release in the absence of T cells. These results suggest that direct interaction of immunoglobulins with monocytes via FcR may represent an important phase of the pathophysiology of adverse reactions to systemic monoclonal antibodies.
Hoffman
T
T
Laboratory of Cell Biology, U.S. Food and Drug Administration, Bethesda, MD 20892.
Tripathi
A K
AK
Lee
Y L
YL
Bonvini
E
E
Golding
B
B
D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology*; D007375:Interleukin-1 / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology*; D011940:Receptor Aggregation; D011961:Receptors, Fc / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007136:Immunoglobulins; D007375:Interleukin-1; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides