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J Biol Chem, Vol. 275, Issue 20, 14903-14909, May 19, 2000
From the Resistance to Gram-negative infection can be
induced by pretreating animals with several agents such as turpentine
and interleukin (IL)-1. Because these agents are powerful inducers of
acute phase proteins, we wondered whether these proteins, more
particularly
Involvement of the Acute Phase Protein
1-Acid
Glycoprotein in Nonspecific Resistance to a Lethal Gram-negative
Infection*
§,
¶,
,

Department of Molecular Biology, Flanders
Interuniversity Institute for Biotechnology and University of Ghent,
9000 Ghent, Belgium, the
Department of Biological Sciences,
University of South Carolina, Columbia, South Carolina 29208, and the
** Department of Molecular and Cellular Biology, Roswell Park Cancer
Institute, Buffalo, New York 14263
1-acid glycoprotein
(
1-AGP), are involved in nonspecific resistance to
infection. Turpentine and IL-1 protect completely against a lethal
challenge of Klebsiella pneumoniae when given 48 and 12-48 h before the challenge, respectively.
1-AGP induction in
the serum reached peak values 48 h after turpentine and 12-48 h
after IL-1 injection. Administration of
1-AGP, 2 h
before a challenge of K. pneumoniae, significantly
increased the survival. Numbers of bacteria cultured from blood and
organs were significantly lower in mice pretreated with a protective
dose of turpentine, IL-1, or
1-AGP. These data suggest
that
1-AGP is a possible mediator in turpentine- or
IL-1-induced protection because time points of maximal induction of
1-AGP by turpentine or IL-1 and of optimal protection by
1-AGP coincide. Transgenic overexpression of rat
1-AGP protected mice from a K. pneumoniae
infection. Bacterial counts in blood and organs were significantly
lower in transgenic mice, and only in control mice were large necrotic
areas, apoptosis, and blood clots observed in the spleen. Our data
suggest that
1-AGP prevents Gram-negative infections and
may be an essential component in nonspecific resistance to infection.
*
This work was supported in part by the Fonds voor
Wetenschappelijk Onderzoek-Vlaanderen Grant G023698N Algemene Spaar en
Lijfrentekas and the Interuniversitaire Attractiepolen.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 Molecular
Biology, K. L. Ledeganckstraat 35, B-9000 Ghent, Belgium. Tel.: 32-9264-8770; Fax: 32-9264-5348; E-mail: claude@dmb.rug.ac.be.
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