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TSG‐14 transgenic mice have improved survival to endotoxemia and to CLP‐induced sepsis
Author(s) -
Dias Adriana A. M.,
Goodman Adam R.,
Dos Santos Jane Lima,
Gomes Rachel Novaes,
Altmeyer Anne,
Bozza Patrícia T.,
de Fátima Horta Maria,
Vilcek Jan,
Reis Luiz F. L.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.6.928
Subject(s) - biology , transgene , genetically modified mouse , tumor necrosis factor alpha , serum amyloid p component , inflammation , sepsis , lipopolysaccharide , immunology , microbiology and biotechnology , in vivo , cytokine , gene , c reactive protein , biochemistry , genetics
Tumor necrosis factor‐stimulated gene 14 (TSG‐14)/PTX3 was identifiedoriginally as a TNF‐α and IL‐1β‐stimulated gene from normal, humanforeskin fibroblasts and vascular endothelial cells, respectively. TSG‐14 gene encodes a 42‐kDa‐secreted glycoprotein with acarboxy‐terminal half that shares homology with the entire sequence of C‐reactive protein (CRP) and serum amyloid P component (SAP),acute‐phase proteins of the pentraxin family. Some experimentalevidence suggests that TSG‐14 plays a role in inflammation, yet itsfunction and mechanism of action remain unclear. We have generatedtransgenic mice that overexpress the murine TSG‐14 gene under thecontrol of its own promoter. From eight transgenic founders, twolineages were derived and better characterized: Tg2 and Tg4, carryingtwo and four copies of the transgene, respectively. TSG‐14 transgenicmice were found to be more resistant to the endotoxic shock induced byLPS and to the polymicrobial sepsis caused by cecal ligation andpuncture (CLP). Moreover, macrophages derived from the transgenic miceproduced higher amounts of nitric oxide in response to IFN‐γ,TNF‐α, and LPS as compared with macrophages from wild‐type animals, and the augmented response appears to be the consequence of a higherresponsiveness of transgenic macrophages to IFN‐γ. The data shownhere are the first in vivo evidence of the involvement of TSG‐14 in the inflammatory process and suggest a role for TSG‐14 in thedefense against bacterial infections.