WO1999064586A2 - Procede d'analyse phagocytaire - Google Patents

Procede d'analyse phagocytaire Download PDF

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Publication number
WO1999064586A2
WO1999064586A2 PCT/EP1999/004043 EP9904043W WO9964586A2 WO 1999064586 A2 WO1999064586 A2 WO 1999064586A2 EP 9904043 W EP9904043 W EP 9904043W WO 9964586 A2 WO9964586 A2 WO 9964586A2
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WO
WIPO (PCT)
Prior art keywords
cell
apoptotic
cells
sequence
compound
Prior art date
Application number
PCT/EP1999/004043
Other languages
English (en)
Other versions
WO1999064586A3 (fr
Inventor
Elke Smits
Wim Maria Rene Van Criekinge
Thierry Andre Oliver Eddy Bogaert
Original Assignee
Devgen N.V.
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
Priority claimed from GBGB9812660.0A external-priority patent/GB9812660D0/en
Priority claimed from GBGB9820816.8A external-priority patent/GB9820816D0/en
Priority to IL14001699A priority Critical patent/IL140016A0/xx
Priority to CA002332993A priority patent/CA2332993A1/fr
Priority to BR9911097-0A priority patent/BR9911097A/pt
Priority to JP2000553576A priority patent/JP2002517238A/ja
Application filed by Devgen N.V. filed Critical Devgen N.V.
Priority to HU0102349A priority patent/HUP0102349A2/hu
Priority to KR1020007014063A priority patent/KR20010071453A/ko
Priority to AU46084/99A priority patent/AU4608499A/en
Priority to EP99929185A priority patent/EP1084242A2/fr
Publication of WO1999064586A2 publication Critical patent/WO1999064586A2/fr
Publication of WO1999064586A3 publication Critical patent/WO1999064586A3/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
    • C07K14/43536—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms
    • C07K14/4354—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms from nematodes
    • C07K14/43545—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms from nematodes from Caenorhabditis
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)

Definitions

  • the expression vector of the invention comprises a sequence of nucleotides encoding a reporter gene positioned so that expression of hlCED-6 or h2CED-6 results in expression of the reporter gene.
  • the reporter gene may be positioned 3' or 5' to said hlced-6 or h2ced-6 and may be expressed as a fusion protein with hlCED-6 or h2CED-6.
  • Suitable reporter genes are those which express a fluorescent product such as green fluorescent protein (GFP) .
  • Other suitable reporter genes are enzymes, such as ⁇ -galactosidase or luciferase, which are capable of acting on a substrate to produce a detectable product, for example a fluorescent product or luminescent product.
  • Examples of expression vectors in accordance with the invention are pGA3103 and pGA3104 which are shown in Figures 29 and 10 respectively.
  • the mammalian cell may be selected from COS1, BHK21, L929, CU1, SWISS 3T3, HT144, IMR32, HEPG2, MDCK, MCF7, 293, hela, A549, SW48 or G361 with COS1 cells being particularly preferred.
  • the mammalian cell is a human dermal FIB, dermal keractinocyte, leucocyte, monocyte, hyphocyte, dendritic cell or macrophage.
  • professional phagocytes such as mouse macrophage cell-line J774 or human monocyte cell-line THP-1.
  • FIGURE 20 shows gel stained with antibodies to the epitope EP 990044 as identified in Example 7 and control antibodies Anti-Xpress Ab (Invitrogen, Leek, The Netherlands) and Mouse lg, horseradish peroxidase- linked whole antibody (from sheep) (ECL Western blotting detection reagents and analysis system, Amersham Pharmacia Biotech, UK, England) ;
  • Ba/F3 stably transfected with ⁇ -galactosidase as reporter gene is used as source of apoptotic cells.
  • a suitable plasmid for transfecting Ba/F3 is pcDNA3.1/His/LacZ as shown in Figure 11.
  • Ba/F3 cells which are IL-3 dependent mouse clones (Palacios and Steinmetz, 1985, Cell
  • Ba/F3 cells were monitored by the annexin/propidium iodide labeling Kit from Boeringher- Mannheim (Brussels, Belgium) .
  • Ba/F3 cells are early apoptotic if 20% annexin positive and less than 5% propidium iodide negative.
  • Ba/F3 cells cultured with growth factor IL-3 were used as a negative control.
  • Fusion proteins CED-6-GFP and GFP-CED-6 are both tyrosine phosphorylated. Their molecular weight is 62385.95K which represents the band between 49 and 74K that is stained positive for anti- phosphotyrosine, anti-green fluorescent protein (GFP) and anti-CED-6.
  • the transfected cell-line was used as a positive control in carrying out phagocytosis assays using the protocol of Example 5.
  • the cells are cultured in RPMI 1640 (Life Technologies) with 2mM L-glutamine adjusted to contain 1.5g/L sodium bicarbonate, 4.5g/L glucose, lOmM HEPES and ImM sodium pyruvate, 10% horse serum, 5% fetal bovine serum.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Toxicology (AREA)
  • Wood Science & Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Public Health (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne des procédés d'analyse permettant de déterminer si un composé est un activateur ou un inhibiteur d'une voie de transduction de signaux, qui favorise la phagocytose de cellules en apoptose. Ces procédés consistent à exposer un phagocyte à des cellules en apoptose, éventuellement transfectées par un gène reporter, et à mesurer l'extension de la phagocytose en présence ou en l'absence du composé de test. Des vecteurs d'expression assurent la transfection de cellules de mammifère avec des séquences d'ADN, qui lorsqu'elles sont exprimées, influencent le taux de phagocytose des cellules en apoptose telles que l'homologue humain du gène ced-6 $i (C. elegans).
PCT/EP1999/004043 1998-06-11 1999-06-10 Procede d'analyse phagocytaire WO1999064586A2 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
EP99929185A EP1084242A2 (fr) 1998-06-11 1999-06-10 Procede d'analyse phagocytaire
AU46084/99A AU4608499A (en) 1998-06-11 1999-06-10 Phagocytic assay method
CA002332993A CA2332993A1 (fr) 1998-06-11 1999-06-10 Procede d'analyse phagocytaire
BR9911097-0A BR9911097A (pt) 1998-06-11 1999-06-10 Método para ensaio fagocìtico
JP2000553576A JP2002517238A (ja) 1998-06-11 1999-06-10 食作用アッセイ方法
IL14001699A IL140016A0 (en) 1998-06-11 1999-06-10 Expression vectors, mammalian cell-lines transfected therewith and assay methods utilizing the same
HU0102349A HUP0102349A2 (hu) 1998-06-11 1999-06-10 Fagocita vizsgálati módszer
KR1020007014063A KR20010071453A (ko) 1998-06-11 1999-06-10 식세포의 분석 방법

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GBGB9812660.0A GB9812660D0 (en) 1998-06-11 1998-06-11 Engulfment gene and uses thereof
GB9812660.0 1998-06-11
GBGB9820816.8A GB9820816D0 (en) 1998-09-24 1998-09-24 Engulfment gene and uses thereof
GB9820816.8 1998-09-24

Publications (2)

Publication Number Publication Date
WO1999064586A2 true WO1999064586A2 (fr) 1999-12-16
WO1999064586A3 WO1999064586A3 (fr) 2000-04-27

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Application Number Title Priority Date Filing Date
PCT/EP1999/004043 WO1999064586A2 (fr) 1998-06-11 1999-06-10 Procede d'analyse phagocytaire

Country Status (11)

Country Link
EP (1) EP1084242A2 (fr)
JP (1) JP2002517238A (fr)
KR (1) KR20010071453A (fr)
CN (1) CN1305525A (fr)
AU (1) AU4608499A (fr)
BR (1) BR9911097A (fr)
CA (1) CA2332993A1 (fr)
HU (1) HUP0102349A2 (fr)
IL (1) IL140016A0 (fr)
PL (1) PL345951A1 (fr)
WO (1) WO1999064586A2 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6316690B1 (en) 1999-08-04 2001-11-13 Tosk, Inc. Non-mammalian transgenic animal model for cellular proliferative diseases
WO2001085207A2 (fr) * 2000-05-05 2001-11-15 The Rockefeller University Modulation de traitement d'antigenes
US6489535B1 (en) 1999-03-18 2002-12-03 The Board Of Trustees Of The Leland Stanford Junior University Non-mammalian transgenic animal having an adult onset neurodegenerative phenotype
US6855504B2 (en) 1999-08-04 2005-02-15 Tosk, Inc. In vivo high throughput toxicology screening method
US7491810B2 (en) * 2001-11-30 2009-02-17 U.S. Department Of Veterans Affairs Transgenic screen and method for screening modulators of brain-derived neurotrophic factor (BDNF) production
US7615676B2 (en) 2001-11-30 2009-11-10 U.S. Department Of Veterans Affairs Transgenic screen and method for screening modulators of brain-derived neurotrophic factor (BDNF) production

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018212612A1 (fr) * 2017-05-17 2018-11-22 울산과학기술원 Procédé et dispositif pour évaluer des cellules immunitaires au moyen de particules magnétiques
KR102213080B1 (ko) * 2017-05-17 2021-02-08 울산과학기술원 자성 입자를 이용한 면역세포의 평가방법

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993020237A1 (fr) * 1992-04-01 1993-10-14 Cambridge Neuroscience, Inc. Clonage par homologie

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993020237A1 (fr) * 1992-04-01 1993-10-14 Cambridge Neuroscience, Inc. Clonage par homologie

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
DRISCOLL, M.: "cell death in C. elegans: molecular insights into mechanisms conserved between nematodes and mammals" BRAIN PATHOLOGY, vol. 6, 1996, pages 411-425, XP002105768 *
ELLIS, R.E., ET AL.: "genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans" GENETICS, vol. 129, September 1991 (1991-09), pages 79-94, XP002105767 cited in the application *
LIU, Q.A., AND HENGARTNER, M.O.: "human CED-6 encodes a functional homologue of the Caenorhabditis elegans engulfment protein CED-6" CURRENT BIOLOGY, vol. 9, no. 22, 18 November 1999 (1999-11-18), pages 1347-1350, XP000879276 *
LIU, Q.A., ET AL.: "candidate adaptor protein CED-6 promotes the engulfment of apoptotic cells in C. elegans" CELL, vol. 93, June 1998 (1998-06), pages 961-972, XP002105771 *
LUCIANI MF. ET AL. : "The ATP binding cassette transporter ABC1, is required for the engulfment corpses generated by apoptotic cell death." EMBO J 1996 JAN 15;15(2):226-35, XP002130461 *
NAGASE T ET AL: "PREDICTION OF THE CODING SEQUENCES OF UNIDENTIFIED HUMAN GENES VI. THE CODING SEQUENCES OF 80 NEW GENES (KIAA0201-KIAA0280) DEDUCED BY ANALYSIS OF CDNA CLONES FROM CELL LINE KG-1 AND BRAIN" DNA RESEARCH, vol. 3, no. 5, 1 January 1996 (1996-01-01), pages 321-329, XP002068376 *
RAMESH, N., ET AL.: "WIP, a protein associated with Wiskott-Aldrich syndrome protein, induces actin polymerisation and redistribution in lymphoid cells" PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE USA, vol. 94, 1997, pages 14671-14676, XP002105769 *
SMITS, E., ET AL. : "the human homologue of Caenorhabditis elegans CED-6 specifically promotes phagocytosis of apoptotic cells" CURRENT BIOLOGY, vol. 9, no. 22, 18 November 1999 (1999-11-18), pages 1351-1354, XP000879275 *
WU,Y.C. AND HORVITZ, H.R.: "C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180" NATURE, vol. 392, no. 6675, 2 April 1998 (1998-04-02), pages 501-504, XP002130460 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6489535B1 (en) 1999-03-18 2002-12-03 The Board Of Trustees Of The Leland Stanford Junior University Non-mammalian transgenic animal having an adult onset neurodegenerative phenotype
US6316690B1 (en) 1999-08-04 2001-11-13 Tosk, Inc. Non-mammalian transgenic animal model for cellular proliferative diseases
US6855504B2 (en) 1999-08-04 2005-02-15 Tosk, Inc. In vivo high throughput toxicology screening method
WO2001085207A2 (fr) * 2000-05-05 2001-11-15 The Rockefeller University Modulation de traitement d'antigenes
WO2001085207A3 (fr) * 2000-05-05 2002-07-11 Univ Rockefeller Modulation de traitement d'antigenes
US7491810B2 (en) * 2001-11-30 2009-02-17 U.S. Department Of Veterans Affairs Transgenic screen and method for screening modulators of brain-derived neurotrophic factor (BDNF) production
US7615676B2 (en) 2001-11-30 2009-11-10 U.S. Department Of Veterans Affairs Transgenic screen and method for screening modulators of brain-derived neurotrophic factor (BDNF) production

Also Published As

Publication number Publication date
BR9911097A (pt) 2001-02-13
PL345951A1 (en) 2002-01-14
CA2332993A1 (fr) 1999-12-16
WO1999064586A3 (fr) 2000-04-27
IL140016A0 (en) 2002-02-10
HUP0102349A2 (hu) 2001-10-28
EP1084242A2 (fr) 2001-03-21
KR20010071453A (ko) 2001-07-28
AU4608499A (en) 1999-12-30
JP2002517238A (ja) 2002-06-18
CN1305525A (zh) 2001-07-25

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