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Inhibition of human lymphocyte proliferation and interleukin 2 production by platelet activating factor (PAF-acether): reversal by a specific antagonist, BN 52021
Authors:M Rola-Pleszczynski  B Pignol  C Pouliot  P Braquet
Institution:1. Immunology Division, Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, QC, Canada J1H 5N4;2. Institut Henri Beaufour Research Laboratories, 17 avenue Descartes, 92350 Le Plessis-Robinson, France;1. Internal Medicine, Hospital Gregorio Marañón, Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain;2. Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain;3. Instituto de investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain;4. Instituto Biología y Genética Molecular, CSIC-UVA, Valladolid, Spain;1. Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, No 1139 Shifu Road, Jiaojiang District, Taizhou 318000, China;2. Weifang Centers for Disease Control and Prevention, No 4801 Huixian Road, Gaoxin Distric, Weifang 261061, Shandong Province, China;3. Municipal Hospital Affiliated to Medical School of Taizhou University, No 381, Zhongshan East Road, Jiaojiang District, Taizhou 318000, China;4. Department of Laboratory Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, NO. 44 Xiaoheyan Road, Dadong District, Shenyang 110042, China;1. Department of Life Sciences, Kyonggi University, Suwon 16227, Republic of Korea;2. Department of Life Science, Gachon University, Seongnam 13120, Republic of Korea
Abstract:When added to a 72 h culture of human peripheral blood mononuclear leukocytes stimulated with phytohemagglutinin, PAF-acether caused a significant inhibition (40-65%) of proliferation at concentrations of 10(-8) to 10(-6) M. This inhibition was reversed by the specific PAF antagonist, BN 52021. It was also reversed by indomethacin, suggesting that PAF-acether mediated this suppression via cyclooxygenase metabolites of arachidonic acid. IL-2 production, measured at 24 h of lymphocyte proliferation, was similarly impaired (50-66%) by 10(-8)-10(-6) M PAF-acether. IL-2 production was brought up to 90% of control values when both PAF-acether and BN 52021 (10(-4) M) were added together to the lymphocyte cultures. These studies suggest a significant immunoregulatory role for PAF-acether and a potential use of BN 52021 as a biological response modifier.
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