The latest...
Stefan Meuer: dkfz-heidelberg.de
dkfz-heidelberg.de
He leads the scientists who've done fundamental research around WF10. The Dr. Guntermann is familiar with WF10.
It'll still take a while.
1: Cell Immunol. 2004 Jun;229(2):149-58.
Differential effects on innate versus adaptive immune responses by WF10.
Giese T, McGrath MS, Stumm S, Schempp H, Elstner E, Meuer SC.
Institute of Immunology, School of Medicine, University of Heidelberg, Im Neuenheimer feld 305, 69120 Heidelberg, Germany. Thomas.Giese@urz.uni-heidelberg.de
Oxidative compounds that are physiologically generated in vivo can induce natural defense mechanisms to enhance the elimination of pathogens and to limit inflammatory tissue damage in the course of inflammation. Here, we have investigated WF10, a chlorite-based non-toxic compound for its functional activities on human PBMC in vitro. WF10 exerts potent immune-modulatory effects through generating endogenous oxidative compounds such as taurine chloramine. Proliferation and IL-2 production of anti-CD3 stimulated PBMC were inhibited by WF10, as was the nuclear translocation of the transcription factor NFATc. In PBMC and monocytes, however, WF10 induced pro-inflammatory cytokines like IL-1beta, IL-8, and TNF-alpha. In the monocytic cell line THP-1, the activation of the transcription factors AP-1 and NFkappaB by WF10 was demonstrated. Inhibition of NFAT regulated genes in activated lymphocytes in concert with the induction of several myeloid cell associated pro-inflammatory genes in monocytes represents a novel mechanism of immune modulation.
1: Free Radic Biol Med. 2004 Nov 15;37(10):1622-30.
Chlorine transfer between glycine, taurine, and histamine: reaction rates and impact on cellular reactivity.
Peskin AV, Midwinter RG, Harwood DT, Winterbourn CC.
Free Radical Research, Department of Pathology, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand. alexander.peskin@chmeds.ac.nz
Hypochlorous acid formed by activated neutrophils reacts with amines to produce chloramines. Chloramines vary in stability, reactivity, and cell permeability. We have examined whether chloramine exchange occurs between physiologically important amines or amino acids and if this affects interactions of chloramines with cells. We have demonstrated transchlorination reactions between histamine, glycine, and taurine chloramines by measuring chloramine decay rates with mixtures as well as by mass spectrometry. Kinetic analysis suggested the formation of an intermediate complex with a high K(m). Apparent second-order rate constants, determined for concentrations <K(m), were 19.4, 23.8, 6.0, and 7.5 M(-1) min(-1) for glycine chloramine (Gly-Cl) and taurine, Gly-Cl and histamine, histamine chloramine and glycine, and taurine chloramine (Tau-Cl) and glycine, respectively. Thus with 10 mM amine concentrations, half-lives for chloramine exchange are on the order of a few minutes. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity in cells was measured as an indicator of permeability of the chloramines. When endothelial or Jurkat cells were treated in Hanks' buffer, Gly-Cl inhibited GAPDH, whereas Tau-Cl, which does not penetrate the cells, did not. Adding glycine to Tau-Cl brought about inhibition, whereas taurine mitigated the effect of Gly-Cl. For cells in full medium, high chloramine concentrations were needed to inhibit GAPDH because of scavenging by methionine and other constituents. In methionine-free medium, chlorine exchange resulted in GAPDH inhibition by Tau-Cl, whereas Gly-Cl was less effective than in Hanks' buffer. Thus interchange between chloramines occurs readily and modulates their cellular effects. |
