Receptor-mediated and lectin-like activities of carp (Cyprinus carpio) TNF-alpha.
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.
Forlenza
Maria
M
Cell Biology and Immunology Group, Wageningen Institute of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
Magez
Stefan
S
Scharsack
Jörn P
JP
Westphal
Adrie
A
Savelkoul
Huub F J
HF
Wiegertjes
Geert F
GF
D000595:Amino Acid Sequence; D000818:Animals; D002347:Carps / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D002465:Cell Movement / Q000502:physiology; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D005393:Fish Diseases / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D015870:Gene Expression; D037102:Lectins / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D010431:Pentoxifylline / Q000494:pharmacology; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D010587:Phagocytosis / Q000276:immunology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D016415:Sequence Alignment; D014352:Trypanosomiasis / Q000276:immunology / Q000662:veterinary*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology; D015854:Up-Regulation / Q000276:immunology
D037102:Lectins; D010726:Phosphodiesterase Inhibitors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline