@article{8131872,
  abstract     = {{Functional characterization of TNF-alpha in species other than mammalian vertebrates is limited, and TNF-alpha has been studied in a limited number of fish species, primarily in vitro using recombinant proteins. Studies on TNF-alpha from different fish species so far pointed to several inconsistencies, in particular with respect to some receptor-mediated activities of fish TNF-alpha, such as the ability to directly activate phagocytes. In the present study a comprehensive analysis of in vitro as well as in vivo biological activities of two isoforms of carp TNF-alpha was performed. Our results show that carp TNF-alpha directly primes carp phagocytes and indirectly promotes typical receptor-mediated activities such as phagocyte activation by acting via endothelial cells. Additionally, for the first time in nonmammalian vertebrate species, the lectin-like activity of fish TNF-alpha homologs; was investigated. Our results show an evolutionary conservation of function of this receptor-independent activity of TNF-alpha not only in cyprinid fish, but also in perciform and salmonid fish. The role of TNF-alpha in vivo, during infections of carp with the blood parasite Trypanoplasma borreli, was examined using three fundamentally different but complementary approaches: (1) inhibition of TNF-alpha expression, (2) overexpression of TNF-alpha, and (3) inhibition of shedding of membrane-bound TNF-alpha. Our results show that, also in fish, a tight regulation of TNF-alpha expression is important, since depletion or excess of TNF-alpha can make an important difference to survival of infection. Finally, we demonstrate a crucial protective role for membrane-bound TNF-alpha, which has a yet unexploited function in fish. The Journal of Immunology, 2009, 183: 5319-5332.}},
  author       = {{Forlenza, M and Magez, Stefan and Scharsack, JP and Westphal, A and Savelkoul, HFJ and Wiegertjes, GF}},
  issn         = {{0022-1767}},
  journal      = {{JOURNAL OF IMMUNOLOGY}},
  keywords     = {{TUMOR-NECROSIS-FACTOR,PERIPHERAL-BLOOD LYMPHOCYTES,SALMON SALMO-SALAR,EXPRESSION ANALYSIS,MOLECULAR-CLONING,RAINBOW-TROUT,TRYPANOPLASMA-BORRELI,NITRIC-OXIDE,ONCORHYNCHUS-MYKISS,TRYPANOSOMA-BRUCEI}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{5319--5332}},
  title        = {{Receptor-mediated and lectin-like activities of carp (cyprinus carpio) TNF-alpha}},
  url          = {{http://doi.org/10.4049/jimmunol.0901780}},
  volume       = {{183}},
  year         = {{2009}},
}

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