|
Originally published In Press as doi:10.1074/jbc.M203832200 on May 22, 2002
J. Biol. Chem., Vol. 277, Issue 29, 26540-26546, July 19, 2002
Detection of Circulating and Endothelial Cell Polymers
of Z and Wild Type 1-Antitrypsin by a Monoclonal Antibody*
Sabina
Janciauskiene §,
Ruta
Dominaitiene ,
Nils H.
Sternby¶,
Eva
Piitulainen , and
Sten
Eriksson
From the Departments of Internal Medicine,
¶ Pathology, and Respiratory Medicine, University Hospital,
Malmö, 20502 Malmö, Sweden
Globular inclusions of abnormal 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.
§
To whom correspondence should be addressed: Dept. of Medicine,
Wallenberg Laboratory, Ing. 46, UMAS, S-20502, Malmö, Sweden. Tel.: 46-40-33-14-14; Fax: 46-40-33-40-71; E-mail:
sabina.janciauskiene@medforsk.mas.lu.se.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
Y.-P. Chang, R. Mahadeva, W.-S. W. Chang, A. Shukla, T. R. Dafforn, and Y.-H. Chu
Identification of a 4-mer Peptide Inhibitor that Effectively Blocks the Polymerization of Pathogenic Z {alpha}1-Antitrypsin
Am. J. Respir. Cell Mol. Biol.,
November 1, 2006;
35(5):
540 - 548.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Persson, D. Subramaniyam, T. Stevens, and S. Janciauskiene
Do Native and Polymeric α1-Antitrypsin Activate Human Neutrophils In Vitro?
Chest,
June 1, 2006;
129(6):
1683 - 1692.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Onda, D. Belorgey, L. K. Sharp, and D. A. Lomas
Latent S49P Neuroserpin Forms Polymers in the Dementia Familial Encephalopathy with Neuroserpin Inclusion Bodies
J. Biol. Chem.,
April 8, 2005;
280(14):
13735 - 13741.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Mahadeva, C. Atkinson, Z. Li, S. Stewart, S. Janciauskiene, D. G. Kelley, J. Parmar, R. Pitman, S. D. Shapiro, and D. A. Lomas
Polymers of Z {alpha}1-Antitrypsin Co-Localize with Neutrophils in Emphysematous Alveoli and Are Chemotactic in Vivo
Am. J. Pathol.,
February 1, 2005;
166(2):
377 - 386.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Gershagen and S. Janciauskiene
ELISA for Specific Detection of PiZ-Related {alpha}1-Antitrypsin Deficiency
Clin. Chem.,
December 1, 2004;
50(12):
2407 - 2410.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D A Lomas and H Parfrey
{alpha}1-Antitrypsin deficiency * 4: Molecular pathophysiology
Thorax,
June 1, 2004;
59(6):
529 - 535.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. T. Mulgrew, C. C. Taggart, M. W. Lawless, C. M. Greene, M. L. Brantly, S. J. O'Neill, and N. G. McElvaney
Z {alpha}1-Antitrypsin Polymerizes in the Lung and Acts as a Neutrophil Chemoattractant
Chest,
May 1, 2004;
125(5):
1952 - 1957.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Parfrey, R. Mahadeva, N. A. Ravenhill, A. Zhou, T. R. Dafforn, R. C. Foreman, and D. A. Lomas
Targeting a Surface Cavity of {alpha}1-Antitrypsin to Prevent Conformational Disease
J. Biol. Chem.,
August 29, 2003;
278(35):
33060 - 33066.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V. Picard, M.-D. Dautzenberg, B. O. Villoutreix, G. Orliaguet, M. Alhenc-Gelas, and M. Aiach
Antithrombin Phe229Leu: a new homozygous variant leading to spontaneous antithrombin polymerization in vivo associated with severe childhood thrombosis
Blood,
August 1, 2003;
102(3):
919 - 925.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|