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J. Biol. Chem., Vol. 277, Issue 29, 26540-26546, July 19, 2002
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From the Departments of Globular inclusions of abnormal
Detection of Circulating and Endothelial Cell Polymers
of Z and Wild Type
1-Antitrypsin by a Monoclonal Antibody*
§,,
, and
Internal Medicine,
¶ Pathology, and Respiratory Medicine, University Hospital,
Malmö, 20502 Malmö, Sweden
1-antitrypsin
(AAT) in the endoplasmic reticulum of hepatocytes are a characteristic
feature of AAT deficiency of the PiZZ phenotype. Monoclonal
antibodies, which contain constant specificity and affinity, are often
used for the identification of Z-mutation carriers. A mouse
monoclonal antibody (ATZ11) raised against PiZZ hepatocytic AAT was
successfully used in enzyme-linked immunosorbent assays (ELISA) and in
identification of Z-related AAT globular inclusions by
immunohistochemical techniques. Using electrophoresis, Western
blotting, and ELISA procedures, we have shown in the present study that
this monoclonal antibody specifically detects a
conformation-dependent neoepitope on both polymerized and
elastase-complexed molecular forms of AAT. The antibody has no apparent
affinity for native, latent, or cleaved forms of AAT. The antibody
ATZ11 illustrates the structural resemblance between the polymerized
form of AAT and its complex with elastase and provides evidence that
Z-homozygotes beyond the native form may have at least one more
circulating molecular form of AAT, i.e. its polymerized
form. In addition, staining of endothelial cells with ATZ11 antibody in
both M- and Z-AAT individuals shows that AAT attached to endothelial
cells is in a polymerized form. The antibody can be a powerful
tool for the study of the molecular profile of AAT, not only in
Z-deficiency cases but also in other (patho)physiological conditions.
*
This work was funded in part by the Swedish Medical Research
Council (K01-72X), the Medical Faculty of Lund University, and the Tore
Nilsson and Alfred Österlund Foundations.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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