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Lymphokines production by concanavalin A-stimulated mouse splenocytes: modulation by Met-enkephalin and a related peptide
Institution:1. Division of Microbiology, Central Drug Research Institute, Post Box No. 173, Lucknow-226 001, India;2. Division of Biopolymers, Central Drug Research Institute, Lucknow, India;3. Division of Pharmacology, Central Drug Research Institute, Lucknow, India;1. Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, United States;2. Jefferson Vaccine Center, Thomas Jefferson University, Philadelphia, PA, United States;1. Institute of Physiology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland;2. Glycom A/S, Kogle Alle 4, 2970 Hørsholm, Denmark;1. Dipartimento STEBICEF, sez. Chimica, Università di Palermo, Viale delle Scienze, Parco d’Orleans II, Ed. 17, 90128 Palermo, Italy;2. Dipartimento di Scienze per la Promozione della Salute e Materno Infantile “G. D’Alessandro”, Area Funzionale di Farmacologia, Università di Palermo, Via del Vespro 129, 90127 Palermo, Italy;3. Dipartimento di Chimica “G. Ciamician”, Università di Bologna, via San Giacomo 11, 40126 Bologna, Italy;4. Dipartimento di Fisica e Chimica, Università di Palermo, Viale delle Scienze, Parco d’Orleans II, Ed. 17, 90128 Palermo, Italy;1. Bacteriology Department, Animal and Plant Health Agency, Addlestone, Surrey KT15 3NB, UK;2. Pest-Tech Ltd., Branch Drain Road, Brookside, RD2 Leeston, New Zealand;3. Connovation Ltd., East Tamaki, Manukau 2013, New Zealand;4. National Wildlife Management Centre, Animal and Plant Health Agency, Woodchester Park, Gloucestershire GL10 3UJ, UK;5. Environment and Sustainability Institute, University of Exeter, Penryn, Cornwall TR10 9EZ, UK;6. School of Veterinary Medicine, Faculty of Health & Medical Sciences, Vet School Main Building, Daphne Jackson Road, University of Surrey, Guildford GU2 7AL, UK
Abstract:Methionine-enkephalin (ME) and its synthetic congener Tyr-D-Ala-Gly-Me-Phe-Gly-NH.C3H7-iso (82/205), in a concentration-dependent biphasic manner modulated the concanavalin A (Con A)-stimulated phagocytosis-promoting (PP)-activity elaboration in the culture supernatants of mouse splenocytes in vitro. Both these peptides at 1 × 10?5 and 1 × 10?6 M inhibited the production of PP activity; conversely, at 1 × 10?7?1 × 10?9 M they augmented it. Peptide 82/205 was nearly 1.2-fold more inhibitory and approximately 1.8-fold more potent in augmenting the PP activity elaboration. The PP activity appeared to be due to lymphokines (LK) gamma interferon and interleukin-4 as the neutralizing concentrations of monoclonal antibodies against these LK significantly (p<0.05) inhibited it. Cycloheximide (50.0 μg/ml) completely inhibited the production of LK indicating their de novo synthesis. The peptides appeared to exert their inhibitory and augmenting effects via δ-and μ-opioid receptors, respectively, as pretreatment of splenocytes with 100-fold higher (1 × 10?3 M) concentration of naloxone was required to block their inhibitory effect; the augmenting effect was blocked by 1 × 10?5 M only. None of the peptides or naloxone could directly stimulate the splenocytes for PP-LK elaboration.
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