Caspase activation is an early event in anthracycline-induced apoptosis and allows detection of apoptotic cells before they are ingested by phagocytes

被引:61
作者
Durrieu, F
Belloc, F
Lacoste, L
Dumain, P
Chabrol, J
Dachary-Prigent, J
Morjani, H
Boisseau, MR
Reiffers, J
Bernard, P
Lacombe, F
机构
[1] Hop Haut Leveque, Hematol Lab, F-33604 Pessac, France
[2] Hop Haut Leveque, CNRS, UMR 5533, F-33604 Pessac, France
[3] Hop Haut Leveque, Serv Malad Sang, F-33604 Pessac, France
[4] UFR Pharm, Lab Spect Biomol, F-51096 Reims, France
关键词
D O I
10.1006/excr.1997.3918
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
An increasing number of methods are being described to detect apoptotic cells. However, attempts to detect apoptotic cells in clinical samples are rarely successful, A hypothesis is that apoptotic cells are cleared from the circulation by phagocytosis before they become detectable by conventional morphological or cytometric methods. Using LR73 adhering cells as phagocytes in a model of in vitro phagocytosis, we found that phagocytosis of daunorubicin (DNR)treated U937, HL60, or K562 leukemia cell lines occurred prior to phosphatidylserine externalization, DNA hydrolysis, chromatin condensation, nuclear fragmentation, or mitochondrial potential alteration. Moreover DNR-treated K562 cells were eliminated by phagocytes while apoptosis was never observed by any of the above methods. By contrast, using a fluorometric batch analysis assay to detect caspase activity in ceramide-or DNR-treated cells (fluorogenic substrate for caspase), we found that caspase activity increased in apoptosis-committed cells before they were detected by flow cytometry or recognized by phagocytes, Similarly a caspase activity increase was detected in circulating mononuclear cells of leukemic patients 15 h after the beginning of anthracyclin treatment. We suggest that recent findings on enzymatic events (caspase activation) occurring in the early events of apoptosis must now allow the development of new markers for apoptosis, irrespective of the morphological features or internucleosomal fragmentation which are late events in apoptosis. (C) 1998 Academic Press.
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页码:165 / 175
页数:11
相关论文
共 44 条
  • [31] Phosphatidylserine externalization is a downstream event of interleukin-1 beta-converting enzyme family protease activation during apoptosis
    Naito, M
    Nagashima, K
    Mashima, T
    Tsuruo, T
    [J]. BLOOD, 1997, 89 (06) : 2060 - 2066
  • [32] PHAGOCYTOSIS OF SENESCENT NEUTROPHILS BY HUMAN MONOCYTE-DERIVED MACROPHAGES AND RABBIT INFLAMMATORY MACROPHAGES
    NEWMAN, SL
    HENSON, JE
    HENSON, PM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1982, 156 (02) : 430 - 442
  • [33] IDENTIFICATION AND INHIBITION OF THE ICE/CED-3 PROTEASE NECESSARY FOR MAMMALIAN APOPTOSIS
    NICHOLSON, DW
    ALI, A
    THORNBERRY, NA
    VAILLANCOURT, JP
    DING, CK
    GALLANT, M
    GAREAU, Y
    GRIFFIN, PR
    LABELLE, M
    LAZEBNIK, YA
    MUNDAY, NA
    RAJU, SM
    SMULSON, ME
    YAMIN, TT
    YU, VL
    MILLER, DK
    [J]. NATURE, 1995, 376 (6535) : 37 - 43
  • [34] The role of proteases during apoptosis
    Patel, T
    Gores, GJ
    Kaufmann, SH
    [J]. FASEB JOURNAL, 1996, 10 (05) : 587 - 597
  • [35] ALTERATIONS IN MITOCHONDRIAL STRUCTURE AND FUNCTION ARE EARLY EVENTS OF DEXAMETHASONE-INDUCED THYMOCYTE APOPTOSIS
    PETIT, PX
    LECOEUR, H
    ZORN, E
    DAUGUET, C
    MIGNOTTE, B
    GOUGEON, ML
    [J]. JOURNAL OF CELL BIOLOGY, 1995, 130 (01) : 157 - 167
  • [36] THROMBOSPONDIN COOPERATES WITH CD36 AND THE VITRONECTIN RECEPTOR IN MACROPHAGE RECOGNITION OF NEUTROPHILS UNDERGOING APOPTOSIS
    SAVILL, J
    HOGG, N
    REN, Y
    HASLETT, C
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (04) : 1513 - 1522
  • [37] MACROPHAGE PHAGOCYTOSIS OF AGING NEUTROPHILS IN INFLAMMATION - PROGRAMMED CELL-DEATH IN THE NEUTROPHIL LEADS TO ITS RECOGNITION BY MACROPHAGES
    SAVILL, JS
    WYLLIE, AH
    HENSON, JE
    WALPORT, MJ
    HENSON, PM
    HASLETT, C
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (03) : 865 - 875
  • [38] SCHURR E, 1989, CANCER RES, V49, P2729
  • [39] ICE-related proteases in apoptosis
    Takahashi, A
    Earnshaw, WC
    [J]. CURRENT OPINION IN GENETICS & DEVELOPMENT, 1996, 6 (01) : 50 - 55
  • [40] COMMITMENT TO APOPTOSIS IS ASSOCIATED WITH CHANGES IN MITOCHONDRIAL BIOGENESIS AND ACTIVITY IN CELL-LINES CONDITIONALLY IMMORTALIZED WITH SIMIAN-VIRUS-40
    VAYSSIERE, JL
    PETIT, PX
    RISLER, Y
    MIGNOTTE, B
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (24) : 11752 - 11756