دورية أكاديمية
Membrane receptor-mediated apoptosis and caspase activation in the differentiated EoL-1 eosinophilic cell line.
العنوان: | Membrane receptor-mediated apoptosis and caspase activation in the differentiated EoL-1 eosinophilic cell line. |
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المؤلفون: | Al-Rabia MW; Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK., Blaylock MG, Sexton DW, Walsh GM |
المصدر: | Journal of leukocyte biology [J Leukoc Biol] 2004 Jun; Vol. 75 (6), pp. 1045-55. Date of Electronic Publication: 2004 Apr 01. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 8405628 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0741-5400 (Print) Linking ISSN: 07415400 NLM ISO Abbreviation: J Leukoc Biol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2023- : Oxford : Oxford University Press Original Publication: New York : Alan R. Liss, c1984- |
مواضيع طبية MeSH: | Cell Differentiation*, Apoptosis/*immunology , Caspases/*metabolism , Eosinophils/*physiology , Leukocyte Common Antigens/*metabolism , fas Receptor/*metabolism, Annexin A5/metabolism ; Caspase Inhibitors ; Cell Line ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Humans ; Leukemia/immunology ; Leukemia/metabolism ; Leukemia/pathology ; Membrane Potentials/drug effects ; Mitochondria/drug effects |
مستخلص: | Caspases are key molecules in the control of apoptosis, but relatively little is known about their contribution to eosinophil apoptosis. We examined caspase-3, -8, and -9 activities in receptor ligation-dependent apoptosis induction in the differentiated human eosinophilic cell line EoL-1. Differentiated EoL-1 exhibited bi-lobed nuclei, eosinophil-associated membrane receptors, and basic granule proteins. Annexin-V fluorescein isothiocyanate binding to EoL-1 revealed significant (P<0.01) apoptosis induction in cells cultured for 20 h with monoclonal antibodies (mAb) specific for CD45 (71%+/-4.3), CD45RA (58%+/-2.3), CD45RB (68%+/-2.4), CD95 (47%+/-2.6), and CD69 (52%+/-2.1) compared with control (23%+/-1.6) or CD45RO mAb (27%+/-3.9). The pan-caspase inhibitor Z-Val-Ala-Asp-fluoromethylketone (fmk) and inhibitors of caspase-8 (Z-Ile-Glu-Thr-Asp-fmk) and caspase-9 (Z-Leu-Glu-His-Asp-fmk) significantly inhibited mAb-induced apoptosis of EoL-1 but had no effect on constitutive (baseline) apoptosis at 16 and 20 h. Caspase activity was analyzed using the novel CaspaTag trade mark technique and flow cytometry. EoL-1 treated with pan-CD45, CD45RA, CD45RB, and CD95 mAb exhibited caspase-3 and -9 activation at 12 h post-treatment, which increased at 16 and 20 h. Activated caspase-8 was detected 12 and 16 h after ligation with CD45, CD45RA, CD45RB, and CD95 mAb followed by a trend toward basal levels at 20 h. CD69 ligation resulted in caspase-3 activation, a modest but significant activation of caspase-8, and a loss in mitochondrial transmembrane potential but had no significant effect on activation of caspase-9. Thus, the intrinsic and extrinsic caspase pathways are involved in controlling receptor ligation-mediated apoptosis induction in human eosinophils, findings that may aid the development of a more targeted, anti-inflammatory therapy for asthma. |
المشرفين على المادة: | 0 (Annexin A5) 0 (Caspase Inhibitors) 0 (Enzyme Inhibitors) 0 (fas Receptor) EC 3.1.3.48 (Leukocyte Common Antigens) EC 3.4.22.- (Caspases) |
تواريخ الأحداث: | Date Created: 20040413 Date Completed: 20040712 Latest Revision: 20171116 |
رمز التحديث: | 20221213 |
DOI: | 10.1189/jlb.0803404 |
PMID: | 15075347 |
قاعدة البيانات: | MEDLINE |
تدمد: | 0741-5400 |
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DOI: | 10.1189/jlb.0803404 |