Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1721-1728
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
Isao Kohno,
Kimiko Inuzuka,
Yumiko Itoh,
Kunihiko Nakahara,
Yutaka Eguchi,
Teruko Sugo,
Gilbu Soe,
Yoichi Sakata,
Hideki Murayama, and
Michio Matsuda
Iatron Laboratories Inc., Katori-Gun, Chiba, Japan; Division of
Hemostasis and Thrombosis Research, Institute of Hematology, Jichi
Medical School, Minamikawachi, Tochigi, Japan; Intensive Care Unit,
Shiga University of Medical Science, Ohtsu, Shiga, Japan.
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
D1, and the epitope of this antibody is located on the
A
(196-204) residue segment. This segment appears to be masked in
fibrin(ogen) but exposed when the A 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.
