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Lymphocyte Activation-31P Magnetic Resonance Studies of Energy Metabolism and Phospholipid Pathways
Affiliation:1. Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso;2. Université de Ouagadougou, Burkina Faso;3. Polytechnic University of Bobo Dioulasso, Burkina Faso;4. Malaria Research and Training Centre, University of Mali, Bamako, Mali;5. Department of Immunology, Wenner-Gren Institute, Stockholm University, Sweden;6. Institute of Immunology and Infection Research, University of Edinburgh, EH9 3JT, Scotland, United Kingdom;7. Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark;8. Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;9. Department of Public Health Sciences, University La Sapienza, Rome, Italy;1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil;2. Universität Konstanz, Konstanz, Germany;1. Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil;2. Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA;3. Fiocruz Piauí, Fundação Oswaldo Cruz, Teresina, PI, Brazil;4. Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, BA, Brazil;5. Instituto Nacional de Ciência e Tecnologia (INCT) de Investigação em Imunologia, Salvador, BA, Brazil;1. Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá D.C., Colombia;2. Universidad del Rosario, Bogotá D.C., Colombia;3. Universidad de Ciencias Aplicadas y Ambientales (UDCA), Bogotá, Colombia;4. Universidad Nacional de Colombia, Bogotá D.C., Colombia;1. ICMR-National Institute of Malaria Research, Field Unit, Campal, Panaji, Goa 403001, India;2. Institute of Bioinformatics, International Tech Park, Bangalore 560066, India;3. Center for Systems Biology and Molecular Medicine, Yenepoya Research Center, Yenepoya (Deemed to be University), Mangalore 575018, India;4. Manipal Academy of Higher Education, Madhav Nagar, Manipal, 576104, India;5. Department of Microbiology, Goa University, Taleigao Plateau, Goa 403206, India
Abstract:31P NMR spectra of perfused lymphocytes embedded in alginate capsules and activated by interleukin-2 (IL-2) are remarkably different from those of control lymphocytes. The main differences are the appearance and gradual increase of phosphodiester signals, glycerophosphocholine and glycerophosphoethanolamine. These metabolic changes also occur following perfusion with phorbol ester and after incubation with phytohemagglutinin (PHA) and are not dependent on a special growth medium. Nifedipine, a calcium channel blocking drug, inhibits the effects of PHA, but not of IL-2. There are no NMR spectral differences between peripheral lymphocytes, stimulated for 3 weeks, and tumor-infiltrating lymphocytes. Thus, sustained accelerated turnover of phosphatidylcholine (PC) and phosphatidylethanolamine is an inherent feature of the activation process. 31P NMR spectra of lymphocytes are characterized by a low phosphocholine signal. Perfusion studies with high concentrations of choline and the use of dapsone, an inhibitor of phosphocholine cytidyltransferase, indicate that choline kinase plays a key role in regulating PC synthesis in human lymphocytes.
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