Cyclosporin H is a potent and selective competitive antagonist of human basophil activation by N-formyl-methionyl-leucyl-phenylalanine☆,☆☆,★,★★
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Reagents
The following were purchased: C5a and N-t-BOC-methionyl-L-leucyl-phenylalanine (BocMLP) (Sigma Chemical Company, St. Louis, Mo.); N-formyl-methionyl-leucyl-l-phenylalanine (FMLP) (Calbiochem- Behring Co., La Jolla, Calif.); PAF C 16:0 (Biomol, Philadelphia, Pa.); 12-0-tetradecanoyl-phorbol-13-acetate (TPA) (P-L Biochemicals Inc., Milwaukee, Wis.); dextran T 70 (Pharmacia Fine Chemicals, Uppsala, Sweden); tritiated LTC 4 (35.7 Ci/mmol; New England Nuclear, Boston, Mass.); tritiated FMLP (40.5
Effect of CsH and CsA on FMLP-induced histamine release from human basophils
In a first series of experiments we assessed the effects of increasing concentrations of CsA and CsH on histamine release from human basophils induced by FMLP. The concentrations of cyclosporins used (8 to 800 nmol/L) included those reached in vivo during CsA treatment (8 to 300 nmol/L)37 and did not induce spontaneous lactate dehydrogenase or histamine release from basophils (data not shown). Fig. 1, A, shows the results from 11 experiments in which basophils were preincubated (5 minutes at
DISCUSSION
This study demonstrates that nanomolar concentrations of CsH exert a potent antiinflammatory effect by inhibiting the release of preformed and de novo synthesized chemical mediators from human basophils activated by FMLP. Our results are compatible with the hypothesis that the inhibitory effect of CsH on the release of mediators from basophils is mediated by the competitive interaction at the FMLP receptor level. The inhibitory effect of CsH is reversible and can be reversed by preincubation
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Cited by (0)
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From the Division of Clinical Immunology, School of Medicine, University of Naples Federico II.
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Supported in part by grants from the National Research Council (C.N.R.) (Targeted Project F.A.T.M.A.; Subproject Prevention and Control of Disease Factors SP. 2; No. 94.00607.PF41 and 95.00856.PF41) and Ministero Università Ricerca Scientifica e Technologica, Rome, Italy.
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Reprint requests: Gianni Marone, MD, Division of Clinical Immunology and Allergy, University of Naples Federico II, School of Medicine, Via S. Pansini, 5, 80131 Napoli, Italy.
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