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- Title
Immunostimulating activities of the novel peptidomimetic L-glutamyl-histamine.
- Authors
Babizhayev, M. A.; Semiletov, Y. A.; Lul'kin, Y. A.; Sakina, N. L.; Savel'yeva, E. L.; Alimbarova, L. M.; Barinskii, I. P.
- Abstract
An original representative of histamine-containing peptidomimetics L-glutamyl-histamine (L-Glu-Hist) was synthesized and characterized as a cytokine mimic leading to cellular responses of improved specificity. The energy-minimized 3-D conformations of L-Glu-Hist derived from its chemical structure resulted in stabilization for Fe2+ chelating complexes. L-Glu-Hist accelerated the decrease of ferrous iron in the ferrous sulphate solution in a concentration-dependent mode and showed the ferroxidase-like activity at concentrations less than 3 mmin the phenanthroline assay, whereas in the concentration range 3–20 mmL-Glu-Hist restricted the availability of Fe2+ to phenanthroline due to binding of ferrous ions in chelating complexes. L-Glu-Hist showed a stimulatory effect on phosphatidylcholine liposomal peroxidation (LPO) catalysed by the superoxide anion radical (O2)-generating system (Fe2++ ascorbate) at low (less or about 1 mm) L-Glu-Hist concentrations and both revealed the inhibitory effect on LPO in this system of high (∼ 10 mm) L-Glu-Hist concentration. L-Glu-Hist released O2 in concentrations which stimulated[3H]-thymidine incorporation into DNA and proliferation of mouse spleen lymphocytes and mononuclear cells from human blood. The structural peptide-like analogues of L-Glu-Hist such as L-Glu-Trp, carcinine (β-alanylhistamine), but not L-Pro-Glu-Trp were active in stimulating thymidine incorporation and in inducing proliferation of mononuclear cells compared to mitogen concanavalin A at doses 2·5–25·0 µg/ml. Our data provide evidence that L-Glu-Hist may act as a very fast and sensitive trigger for lymphocyte proliferation and immunoregulation.
- Subjects
HISTAMINE; ANTIHISTAMINES; IMIDAZOLES; LECITHIN; PEROXIDATION; ANIONS
- Publication
Clinical & Experimental Immunology, 2005, Vol 139, Issue 3, p447
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1111/j.1365-2249.2004.02710.x