Inhibition of neutrophil oxidative burst by elastase-generated IgG fragments.
IgG1 is cleaved in vitro by granulocyte elastase into Fc, Fab and Fabc fragments. The cleaved products have been isolated by a series of chromatographic procedures and characterized with regard to molecular mass and isoelectric point. The Fc fragment has been previously shown to express at its N-terminal site a neoantigen which is specific for elastase (Kolb, G., Eckle, I., Heidtmann, H.-H., Neurath, F. & Havemann, K. (1988) Scand. J. Rheumatol. S75, 179-189). The production of superoxide radical anions in prestimulated neutrophils is inhibited dose-dependently by the elastase-generated Fc and Fabc fragments. Native IgG1 and Fab fragments show no inhibitory effect, nor do papain-generated Fc fragments. The degree of inhibition depends on the stimulus applied: half-maximal inhibition is obtained by 6 microM Fc after stimulation with 4 beta-phorbol and 2.4 microM after stimulation with fMet-Leu-Phe; neutrophils stimulated with serum-activated zymosan are not inhibited by IgG fragments. The effect of Fc is purely cellular; no inhibition of O2 generation can be produced by applying Fc to the xanthine oxidase/xanthine system. The fragments have no effect on the activation or activity of crude NADPH oxidase, which is the O2-forming enzyme system of neutrophils. Possible mechanisms are discussed by which Fc acts on stimulated neutrophils.
Eckle
I
I
Zentrum für Innere Medizin, Universität Marburg.
Kolb
G
G
Havemann
K
K
D004305:Dose-Response Relationship, Drug; D006801:Humans; D007128:Immunoglobulin Fragments / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000032:analysis / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D010196:Pancreatic Elastase