Oxidation of alpha1-proteinase inhibitor by the myeloperoxidase-hydrogen peroxidase system promotes binding to immunoglobulin A.
We have demonstrated previously that patients with rheumatoid arthritis (RA) show an increase in serum and synovial fluid levels of complexes between alpha1-proteinase inhibitor (alpha1PI) and IgA. These are believed to form through disulfide binding between the Cys232 residue on alpha1PI and the penultimate cysteine residue (Cys471) of the IgA alpha chain. The mechanism for this has not been elucidated. We show here that alpha1PI oxidized by the myeloperoxidase-hydrogen peroxide (MPO-H2O2) system promotes the formation of IgA-alpha1PI complexes when incubated with IgA and that such complexes have no inhibitory activity against porcine pancreatic elastase (PPE). The activity of alpha1PI was considerably reduced also in IgA-alpha1PI complexes isolated from serum of an RA patient. We suggest that formation of IgA-alpha1PI complexes in inflammation may involve oxidation of alpha1PI, and as a consequence the alpha1PI in such complexes has reduced elastase inhibitory activity.
Scott
L J
LJ
Department of Haemopoeitic Cell and Gene Therapy, Paterson Institute for Cancer Research, Christie Hospital, Wilmslow Road, Manchester, M20 4BX, United Kingdom.
Russell
G I
GI
Nixon
N B
NB
Dawes
P T
PT
Mattey
D L
DL
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007070:Immunoglobulin A / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D010084:Oxidation-Reduction; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D009195:Peroxidase / Q000378:metabolism*; D011485:Protein Binding; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013552:Swine; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D007070:Immunoglobulin A; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D006861:Hydrogen Peroxide; D009195:Peroxidase; D010196:Pancreatic Elastase