Characterization of a tumor necrosis factor. alpha. (TNF-. alpha. ) inhibitor: Evidence of immunological cross-reactivity with the TNF receptor
- Hopital Cantonal Universitaire, Geneva (Switzerland)
Previous studies have shown that urine of febrile patients contains a tumor necrosis factor {alpha} inhibiting activity (TNF-{alpha} Inh) when tested in a cytotoxicity assay using the tumor necrosis factor {alpha} (TNF-{alpha})-susceptible cell line L929. In the present study, the authors investigated the relationship between the TNF-{alpha} Inh and a potential soluble form of the receptor, as the former has been shown to block TNF-{alpha} activities by binding to the ligand. They demonstrate that human TNF-{alpha} is affected to a greater extent than is murine TNF-{alpha}. This species specificity of the inhibitor correlates with the binding studies of TNF receptor interactions already reported. They raised a polyclonal antibody to TNF-{alpha} Inh that neutralizes its activity and does not recognize TNF-{alpha}. Solubilized cross-linked {sup 125}I-labeled TNF-{alpha} receptor complex could be immunoprecipitated by using either anti-TNF-{alpha} or anti-TNF-{alpha} Inh antibody, suggesting immunological cross-reactivity between the receptor and the inhibitor. By using fluorescein isothiocyanate-coupled TNF-{alpha}, it was possible to visualize by fluorescence-activated cell sorter analysis the TNF-{alpha} receptor on phytohemagglutinin/interleukin 2-activated T cells. A similar increase of immunofluorescence intensity of the activated T cells was observed by using anti-TNF-{alpha} Inh antibody revealed with a fluorescein isothiocyanate-coupled goat anti-rabbit IgG1 conjugate, suggesting that the TNF-{alpha} Inh is also expressed as a membrane protein. Taken together, their results suggest that the TNF-{alpha} Inh originally described might be a soluble form of the TNF receptor itself.
- OSTI ID:
- 6214363
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:13; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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550201* - Biochemistry- Tracer Techniques