Reactive oxygen product formation after Fc gamma receptor-mediated neutrophil activation by monomeric mouse IgG2a: implications for the generation of first dose effects after OKT3 treatment.
In the present study, we provide evidence that IgG2a monoclonal antibody (mAb) OKT3 is able to induce reactive oxygen intermediate (ROI) formation in polymorphonuclear leukocytes (PMN) when Fc gamma RIIIB as well as Fc gamma RII are bound concomitantly. Inhibition of binding to either Fc gamma R by specific mAb (3G8 or IV.3, respectively) resulted in complete abrogation of the OKT3-induced respiratory burst. The effect of OKT3 was independent from its specificity and thus also from its T cell-activating property, since nonbinding IgG2a isotype controls induced similar amounts of ROI. The IgG2b mAb BMA031 as well as the respective nonbinding isotype control were only minimally effective. With regard to the potential role of PMN activation in inflammation and tissue damage, our findings offer an extended explanation for the generation of initial adverse reactions to OKT3. Thus, one might speculate that the concerted action of cytokines liberated after its administration, what may lead to margination of leukocytes, and activation of PMN via Fc gamma R might produce first-dose reactions to OKT3 by directing radical-mediated damage against the endothelium.
Zlabinger
G J
GJ
Institut für Immunologie, Universität Wien, Austria.
Rosenkranz
A R
AR
Schmaldienst
S
S
Stuhlmeier
K
K
Böhmig
G
G
Stöckl
J
J
Pohanka
E
E
Kovarik
J
J
D000818:Animals; D000918:Antibody Specificity; D002449:Cell Aggregation / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D066298:In Vitro Techniques; D051379:Mice; D016853:Muromonab-CD3 / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017452:Receptors, IgG / Q000502:physiology*; D016897:Respiratory Burst
D007074:Immunoglobulin G; D016853:Muromonab-CD3; D017382:Reactive Oxygen Species; D017452:Receptors, IgG