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WO1993016715A1 - Facteur 1 de stimulation de fibroblastes et detection anticipee de la fibrose - Google Patents

Facteur 1 de stimulation de fibroblastes et detection anticipee de la fibrose Download PDF

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Publication number
WO1993016715A1
WO1993016715A1 PCT/US1993/001554 US9301554W WO9316715A1 WO 1993016715 A1 WO1993016715 A1 WO 1993016715A1 US 9301554 W US9301554 W US 9301554W WO 9316715 A1 WO9316715 A1 WO 9316715A1
Authority
WO
WIPO (PCT)
Prior art keywords
fsf
polypeptide
sample
fibrotic scarring
antibody
Prior art date
Application number
PCT/US1993/001554
Other languages
English (en)
Inventor
David Wyler
Sadhana Prakash
Original Assignee
New England Medical Center Hospitals, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by New England Medical Center Hospitals, Inc. filed Critical New England Medical Center Hospitals, Inc.
Publication of WO1993016715A1 publication Critical patent/WO1993016715A1/fr

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475Growth factors; Growth regulators
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52Cytokines; Lymphokines; Interferons
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • mice Animals and Schistosomiasis infection C57BL/6NcrLBr female mice (18 to 20 g; Taconic Farms, Inc., Germantown, NY) were infected by the intraperitoneal injection of 35-50 cercariae of S. mansoni (Puerto Guatemalan strain) suspended in 0.5 ml sterile saline. The mice were euthanized eight weeks later by inducing C0 2 narcosis and their livers were placed in cold Hanks'' buffered salt solution (HBSS) . Isolation of granulomas and preparation of crranuloma supernatant. Isolation of granulomas was performed as described previously (Wyler et al. , Science.
  • Antibody-treated cells were sorted FACStar Plus flow cytometry and analyzed by a FACScan (Becton- Dickinson) or a Coulter Epics 541 (Coulter Electronics Inc. , Hialeah, FL) flow cytometer. The fields were gaited to exclude autofluorescent and dead cells.
  • the CD4+ sorted cells were washed and suspended (0.6-1.0 x 10 6 /ml) in serum-free medium RPMI 1640 supplemented with 0.3 g/ml bovine serum albumin (BSA; Sigma, St. Louis, MO) and incubated for 24h at 30°C in 5% C0 2 - 95% air humid atmosphere.
  • BSA bovine serum albumin
  • the beads were pelleted (12,000 g x 5 min) , washed twice in phosphate-buffered 0.15 M NaCl and then boiled for 5 min in sample buffer (lOmM Tris-HCl; 2% sodium dodecyl sulfate; 5% glycerol; 2% dithiothreitol; 0.05% pyronin Y; pH 6.8). Supernatant from these treated beads were subjected to electrophoresis in a 70 x 70 x 0.5 ui slab gel of 10% acrylamide (BioRad Labs, Richmond, CA) using standard method (Laemmli, Nature 227:680 (1970)).
  • proteins were transferred electrophoretically (l-2h; 70 volts) onto nitrocellulose paper (BioRad) using standard procedures.
  • the nitrocellulose paper was then exposed to X-ray film (X- OMAT, AR; Kodak, Rochester, NY) for 72 h at -70°C.
  • Anti-FSF-1 antibody detected FSF-1 in both purified form and in crude granuloma supernatant in a dot-blot ELISA assay (Fig. 5) .
  • the antibody did not detect acidic FGF or PDGF, mitogens that were detected with the appropriate homologous antibodies (Fig. 5) .
  • CD4 + cells are stimulated "" in vivo to produce FsF-1 in response to egg antigens. Based on our current observation, such production may continue at least briefly when the lymphocytes are dissociated from the eggs and antigen-presenting cells.
  • FsF-1 not only is secreted but also can remain associated with the surface of CD4 + lymphocytes suggests that in addition to the action of the secreted cytokine, direct contact between membrane-associated FsF-1 positive lymphocytes and fibroblasts might stimulate fibroblast growth.
  • fibroblast growth factors some of which were purified from other sources and were recognized for this biological property (PDGF [Ross et al.. Cell 46:155 (1986)], FGF [Gospodarowicz et al. , J. Biol. Chem. 250:2515 (1975); Gospodarowicz et al. , J. Biol. 253.:3736 (1978)]), and heparin-binding epidermal growth factor [HB-EGF;Higashiyama et al.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Procédé d'identification d'individus susceptibles de présenter une cicatrisation due à la fibrose. Le procédé consiste à prélever un échantillon chez un individu atteint d'une maladie inflammatoire chronique, à mettre l'échantillon en contact avec un anticorps spécifique au facteur 1 de stimulation de fibroblastes (FSF-1) dans des conditions permettant la formation d'un complexe immun, et à détecter l'éventuelle augmentation du taux relatif du complexe immun, laquelle indiquerait une vulnérabilité à la cicatrisation due à la fibrose. On a également prévu des polypeptides de FSF-1 et des anticorps spécifiques au FSF-1.
PCT/US1993/001554 1992-02-24 1993-02-19 Facteur 1 de stimulation de fibroblastes et detection anticipee de la fibrose WO1993016715A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US840,426 1977-10-07
US84042692A 1992-02-24 1992-02-24

Publications (1)

Publication Number Publication Date
WO1993016715A1 true WO1993016715A1 (fr) 1993-09-02

Family

ID=25282348

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1993/001554 WO1993016715A1 (fr) 1992-02-24 1993-02-19 Facteur 1 de stimulation de fibroblastes et detection anticipee de la fibrose

Country Status (1)

Country Link
WO (1) WO1993016715A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996026953A1 (fr) * 1995-02-28 1996-09-06 New England Medical Center Hospitals, Inc. FsF-1 ET LA DETECTION PRECOCE DES FIBROSES
US6017719A (en) * 1994-06-14 2000-01-25 Nexell Therapeutics, Inc. Positive and positive/negative cell selection mediated by peptide release
US6214968B1 (en) 1992-02-24 2001-04-10 New England Medical Center Hospitals, Inc. Fibroblast stimulating growth factor 1 (FsF-1) and the early detection of fibrosis

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
D. CATTY, "Antibodies, Volume 1, A Practical Approach", Published 1989, by IRL PRESS, see pages 19-79. *
JOURNAL OF IMMUNOLOGY, Volume 132, Number 6, issued June 1984, D.J. WYLER et al., "Fibroblast Stimulation in Schistosomiasis", pages 3142-3148. *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6214968B1 (en) 1992-02-24 2001-04-10 New England Medical Center Hospitals, Inc. Fibroblast stimulating growth factor 1 (FsF-1) and the early detection of fibrosis
US6017719A (en) * 1994-06-14 2000-01-25 Nexell Therapeutics, Inc. Positive and positive/negative cell selection mediated by peptide release
WO1996026953A1 (fr) * 1995-02-28 1996-09-06 New England Medical Center Hospitals, Inc. FsF-1 ET LA DETECTION PRECOCE DES FIBROSES
WO1996026954A1 (fr) * 1995-02-28 1996-09-06 New England Medical Center Hospitals, Inc. Fsf-1 et la detection precoce des fibroses

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