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Receptor-mediated and lectin-like activities of carp (Cyprinus carpio) TNF-alpha.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wiegertjes, Geert F. Magez, Stefan Savelkoul, Huub F. J. Forlenza, Maria Westphal, Adrie Scharsack, Jörn P.
Description	Country affiliation: Netherlands Author Affiliation: Forlenza M ( Cell Biology and Immunology Group, Wageningen Institute of Animal Sciences, Wageningen University, Wageningen, The Netherlands.)
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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	8
Volume Number	183
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2009-10-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Carps Immunology Endothelial Cells Fish Diseases Phagocytes Trypanosomiasis Veterinary Tumor Necrosis Factor-alpha Amino Acid Sequence Animals Metabolism Parasitology Cell Movement Physiology Gene Expression Lectins Molecular Sequence Data Pentoxifylline Pharmacology Drug Effects Phagocytosis Phosphodiesterase Inhibitors Recombinant Proteins Sequence Alignment Antagonists & Inhibitors Up-regulation Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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