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.
Eckle
I
I
Centre for Internal Medicine, Philipps University, Marburg, West Germany.
Kolb
G
G
Heiser
C
C
Havemann
K
K
D003571:Cytochalasin B / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D007141:Immunoglobulin Fc Fragments / Q000502:physiology; D007074:Immunoglobulin G / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D012710:Serum Albumin, Bovine; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; D010196:Pancreatic Elastase