A monoclonal antibody specific to the granulocyte-derived elastase-fragment D species of human fibrinogen and fibrin: its application to the measurement of granulocyte-derived elastase digests in plasma.
When granulocytes are stimulated under certain clinical conditions, elastase is released therefrom and digests fibrin(ogen) independently of the plasmin system, which may also be mobilized simultaneously. Thus, discrimination of these 2 systems becomes urgent for the diagnosis and treatment of the underlying diseases. Using as immunogen a 97-kd granulocyte-elastase digest of human fibrinogen, we raised an antibody IF-123 that specifically recognizes elastase digests of human fibrin(ogen). The 97-kd elastase fragment resembles plasmic fragment D(1), and the epitope of this antibody is located on the Aalpha (196-204) residue segment. This segment appears to be masked in fibrin(ogen) but exposed when the Aalpha Leu 204-Ile 205 peptide bond is cleaved by elastase. Cathepsin G concomitantly released from granulocytes failed to expose the epitope. By an enzyme immunoassay using IF-123 as the capture antibody, the elastase digests of fibrin(ogen) can be measured in plasma samples without interference by abundantly coexisting fibrinogen. Indeed, we found that the elastase digests were mostly elevated in patients with inflammation or malignant tumors, but remained in a normal range in patients with a benign gastrointestinal tract disease such as duodenal ulcer and polyps in the gallbladder or the colon. Like the plasmic D-dimer, the elastase digests predominantly consisted of the DD/E complex and DD/E-containing high-molecular weight derivatives apparently corresponding to the phase-3 plasmic digests of cross-linked fibrin. (Blood. 2000;95:1721-1728)
Kohno
I
I
Iatron Laboratories Inc., Katori-Gun, Chiba, Japan.
Inuzuka
K
K
Itoh
Y
Y
Nakahara
K
K
Eguchi
Y
Y
Sugo
T
T
Soe
G
G
Sakata
Y
Y
Murayama
H
H
Matsuda
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis* / Q000276:immunology; D005340:Fibrinogen / Q000378:metabolism*; D005767:Gastrointestinal Diseases / Q000097:blood; D006098:Granulocytes / Q000201:enzymology*; D006801:Humans; D007249:Inflammation / Q000097:blood; D019272:Leukocyte Elastase / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000097:blood
D000911:Antibodies, Monoclonal; D000939:Epitopes; D005338:Fibrin Fibrinogen Degradation Products; D005337:Fibrin; D005340:Fibrinogen; D019272:Leukocyte Elastase