Characterization of a tumor necrosis factor. alpha. (TNF-. alpha. ) inhibitor: Evidence of immunological cross-reactivity with the TNF receptor

Journal Article · Sun Jul 01 04:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.13.5188· OSTI ID:6214363

Seckinger, P; Zhang, Jianhua; Hauptmann, B; Dayer, J M ^[1]

---

1. 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), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:13; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
AROMATICS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
CHEMICAL ACTIVATION
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DYES
ELECTRON CAPTURE RADIOISOTOPES
ELECTROPHORESIS
FLUORESCEIN
HYDROXY ACIDS
HYDROXY COMPOUNDS
INHIBITION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTHIOCYANATES
ISOTOPES
LEUKOCYTES
LYMPHOCYTES
MATERIALS
MEMBRANE PROTEINS
NECROSIS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PATHOLOGICAL CHANGES
PATIENTS
PHENOLS
POLYPHENOLS
PROTEINS
PURIFICATION
RADIOISOTOPES
RECEPTORS
SOMATIC CELLS
URINE
WASTES