Stimulation of neutrophil elastase and myeloperoxidase release by IgG fragments.

Human leucocyte elastase (HLE) cleaves IgG into Fab and Fc fragments. The Fc fragment bears an elastase-specific antigen and has previously been reported to be found in synovial fluid during rheumatoid arthritis. In addition, biological activity of elastase-specific Fc fragments has been described in modulating granulocyte oxidative metabolism. To investigate further regulatory effects of the elastase-induced IgG cleavage products, we tested the elastase and myeloperoxidase release of granulocytes. IgG fragments induce no enzyme release of unstimulated neutrophils. But elastase and myeloperoxidase release of cytochalasin b/FMLP-treated neutrophils is stimulated in a dose-dependent manner by the Fab fragments. The extent of stimulation depends on stimulus concentration and is at its maximum for low (e.g. 2.5 x 10(-8) M) FMLP concentration. Ten nanomoles Fab/4 x 10(6) PMN augment elastase release to 206% and myeloperoxidase release to 155% after pre-stimulation with 2.5 x 10(-8) M FMLP. Fc fragments stimulate elastase release to 162% but no MPO release. Untreated IgG1 and analog Fab and Fc fragments produced by papain cleavage react similarly. Elastase-generated IgG fragments may therefore up-regulate their concentration by simulating elastase release. The concomitantly stimulated release of myeloperoxidase may influence bactericidal activity and termination of oxidative burst.