کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10908742 | 1087802 | 2015 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
LFA-1-targeting Leukotoxin (LtxA; Leukothera®) causes lymphoma tumor regression in a humanized mouse model and requires caspase-8 and Fas to kill malignant lymphocytes
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کلمات کلیدی
MFIWBCFADDLFA-1inflammation - التهاب( توروم) Integrin - اینتگرینAutoimmune disease - بیماری خودایمنیFas Ligand - فاس لیگاندFasL - فاسدLymphocytes - لنفوسیت هاLymphoma - لنفومLeukotoxin - لکوتوکسینCell death - مرگ سلولی mean fluorescence intensity - میانگین شدت فلورسانسFas-associated protein with death domain - پروتئین مرتبط با Fas با دامنه مرگwhite blood cell - گلبول سفید خون
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Leukotoxin (LtxA) is a protein secreted from the oral bacterium Aggregatibacter actinomycetemcomitans. LtxA binds to the β2 integrin lymphocyte-associated function antigen-1 (LFA-1) on human white blood cells (WBCs), resulting in cell death. LtxA is currently under investigation as a novel therapy (Leukothera®) for treating hematologic malignancies and autoimmune diseases. We show here that LtxA has potent in vivo anti-lymphoma activity in mice. LtxA caused complete regression of B-cell tumors and promoted long-term survival of mice. The mechanism of LtxA-mediated killing of malignant lymphocytes was further examined. We found that LtxA kills malignant lymphocytes by a novel mechanism requiring the death receptor Fas and caspase-8, but not Fas ligand (FasL) or caspase-9. We also determined that LFA-1 and Fas are closely associated on the cell surface and this proximity of LFA-1 and Fas could explain how signaling through an integrin can lead to cell death. In addition to LFA-1, this work reveals a second surface protein, Fas, that is critical for LtxA-mediated cell death. Knowledge of the mechanism of cell death induced by LtxA will facilitate the development and understanding of this potent experimental therapeutic agent.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Leukemia Research - Volume 39, Issue 6, June 2015, Pages 649-656
Journal: Leukemia Research - Volume 39, Issue 6, June 2015, Pages 649-656
نویسندگان
Kristina M. DiFranco, Nadine Johnson-Farley, Joseph R. Bertino, David Elson, Brian A. Vega, Benjamin A. Jr., Scott C. Kachlany,