Binding and inhibition of myeloperoxidase (MPO): a major function of ceruloplasmin?
Interactions between plasma proteins and MPO were studied. The protein fraction of normal plasma and serum was shown to exhibit an inhibitory effect on the peroxidase activity of MPO. Most of the inhibitory effect could be retained on an MPO-coupled affinity chromatography column. In particular, a protein with apparent mol. wt of 130 kD showed affinity for MPO. The protein was identified as ceruloplasmin by N-terminal amino acid sequencing and immunochemistry. During separation procedures the peroxidase inhibitory effect was limited to ceruloplasmin-containing fractions of plasma. Purified ceruloplasmin inhibited the peroxidase activity of MPO in a concentration-dependent manner, and exhibited selective binding to MPO-coated microtitre plates. This binding could be inhibited by MPO dissolved in buffer. Correspondingly the binding of MPO to ceruloplasmin-coated plates could be blocked by ceruloplasmin in solution, showing a physical interaction to occur between the two proteins under physiological conditions. We also found affinity to exist between MPO and C3 (and its C3d-containing fragments). However, C3 and C3 fragments did not inhibit the peroxidase reaction in vitro. We propose that ceruloplasmin takes part in the clearance and inactivation of MPO, in vivo. We also speculate that impaired inactivation of MPO may have a pathophysiological role in inflammatory diseases characterized by autoantibodies to MPO, such as rapidly progressive glomerulonephritis with P-ANCA (perinuclear anti-neutrophil cytoplasmic antibodies).
Segelmark
M
M
Department of Nephrology, Lund University, University Hospital, Sweden.
Persson
B
B
Hellmark
T
T
Wieslander
J
J
D002570:Ceruloplasmin / Q000302:isolation & purification / Q000502:physiology*; D002846:Chromatography, Affinity; D006801:Humans; D015151:Immunoblotting; D009195:Peroxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding
D009195:Peroxidase; D002570:Ceruloplasmin