title: Purification and characterization of an inhibitor (soluble tumor necrosis factor receptor) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients.
abstract: Serum ultrafiltrates (SUF) from human patients with different types of cancer contain a blocking factor (BF) that inhibits the cytolytic activity of human tumor necrosis factor alpha (TNF-alpha) in vitro. BF is a protein with a molecular mass of 28 kDa on reducing sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE). The active material was purified to homogeneity by a combination of affinity chromatography, PAGE, and high-pressure liquid chromatography. Amino acid sequence analysis revealed that BF is derived from the membrane TNF receptor. Purified BF blocks the lytic activity of recombinant human and mouse TNF-alpha and recombinant human lymphotoxin on murine L929 cells in vitro. However, BF inhibits the lytic activity of TNF-alpha more effectively than it does that of lymphotoxin. The BF also inhibits the necrotizing activity of recombinant human TNF-alpha when coinjected into established cutaneous Meth A tumors in BALB/c mice. The BF may have an important role in (i) the regulation and control of TNF-alpha and lymphotoxin activity in cancer patients, (ii) interaction between the tumor and the host antitumor mechanisms, and (iii) use of systemically administered TNF-alpha in clinical trials with human cancer patients.
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.
authors.forename: T
authors.initials: T
authors.lastname: Gatanaga
authors.forename: C D
authors.initials: CD
authors.lastname: Hwang
authors.forename: W
authors.initials: W
authors.lastname: Kohr
authors.forename: F
authors.initials: F
authors.lastname: Cappuccini
authors.forename: J A
authors.initials: JA
authors.lastname: Lucci
authors.forename: E W
authors.initials: EW
authors.lastname: Jeffes
authors.forename: R
authors.initials: R
authors.lastname: Lentz
authors.forename: J
authors.initials: J
authors.lastname: Tomich
authors.forename: R S
authors.initials: RS
authors.lastname: Yamamoto
authors.forename: G A
authors.initials: GA
authors.lastname: Granger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008233:Lymphotoxin-alpha / Q000037:antagonists & inhibitors*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009369:Neoplasms / Q000097:blood*; D009374:Neoplasms, Experimental / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood; D011956:Receptors, Cell Surface / Q000302:isolation & purification*; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D008233:Lymphotoxin-alpha; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha