Biphasic granulocytopenia after administration of the first dose of OKT3.
The effects of the administration of OKT3, a second immunoglobulin G2a (IgG2a) anti-CD3 monoclonal antibody (mAb), and its isotype switch variant IgA on granulocyte kinetics were compared for 5 hours after the first administration of the mAb. In addition, in vivo and in vitro studies were performed on alterations in expression of CD11b and CD62L induced by these mAbs. Within 15 minutes after administration OKT3 and IgG2a anti-CD3 mAbs induced a significant decrease in circulating granulocytes, whereas IgA anti-CD3 mAb did not. Apparently the initial decrease in circulating granulocytes depends on the heavy chain of the administered anti-CD3 mAb, resulting in immunocytoadherence and sequestration in the lungs. Increased adherence to pulmonary endothelium by altered expression of CD11b and CD62L plays a minor role in this first granulocytopenia, because each mAb exerted the same effects on these adhesion molecules in vitro. The second decrease in granulocyte counts occurred 60 minutes after administration of each mAb and correlated with a significant increase in expression of CD11b and CD62L in vivo and with upregulation of CD11b and down-regulation of CD62L in vitro. These alterations could be related to the presence of tumor necrosis factor-alpha both in vivo and in vitro. Thus granulocyte kinetics from 30 minutes after administration of each anti-CD3 mAb resemble neutrophil kinetics induced by TNF-alpha.
D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D006098:Granulocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D019041:L-Selectin / Q000276:immunology; D007958:Leukocyte Count / Q000187:drug effects; D016177:Macrophage-1 Antigen / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000009:adverse effects*; D009500:Neutralization Tests; D014184:Transplantation, Homologous / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D016177:Macrophage-1 Antigen; D016853:Muromonab-CD3; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin