A common neoepitope is created when the reactive center of C1-inhibitor is cleaved by plasma kallikrein, activated factor XII fragment, C1 esterase, or neutrophil elastase.
The reactive center of C1-inhibitor, a plasma protease inhibitor that belongs to the serpin superfamily, is located on a peptide loop which is highly susceptible to proteolytic cleavage. With plasma kallikrein, C1s and beta-Factor XIIa, this cleavage occurs at the reactive site residue P1 (Arg444); with neutrophil elastase, it takes place near P1, probably at residue P3 (Val442). After these cleavages, C1-inhibitor is inactivated and its conformation is modified. Moreover, in vivo, cleaved C1-inhibitor is removed from the blood stream more rapidly than the intact serpin, which suggests that proteolysis unmasks sites responsible for cellular recognition and the uptake of the cleaved inhibitor. In the study reported here, we show, using an MAb, that an identical neoepitope is created on C1-inhibitor after the cleavage of its exposed loop by plasma kallikrein, C1s, beta-Factor XIIa, and by neutrophil elastase.
de Agostini
A
A
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232.
Patston
P A
PA
Marottoli
V
V
Carrel
S
S
Harpel
P C
PC
Schapira
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D003166:Complement Activating Enzymes / Q000378:metabolism*; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism* / Q000502:physiology; D003173:Complement C1s / Q000378:metabolism* / Q000502:physiology; D004789:Enzyme Activation; D000939:Epitopes / Q000302:isolation & purification*; D005174:Factor XII / Q000378:metabolism* / Q000502:physiology; D015956:Factor XIIa; D006358:Hot Temperature; D006801:Humans; D007118:Immunoassay; D007610:Kallikreins / Q000097:blood* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism* / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology; D011487:Protein Conformation; D011489:Protein Denaturation; D012697:Serine Endopeptidases / Q000378:metabolism* / Q000502:physiology
D000911:Antibodies, Monoclonal; D003174:Complement C1 Inactivator Proteins; D000939:Epitopes; D010446:Peptide Fragments; D005174:Factor XII; D003166:Complement Activating Enzymes; D007610:Kallikreins; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase; D015956:Factor XIIa; D003173:Complement C1s