Is there a role of taurine bromamine in inflammation? Interactive effects with nitrite and hydrogen peroxide.
OBJECTIVE
The myeloperoxidase system of neutrophils generates chlorinating and brominating oxidants in vivo. The major haloamines of the system are taurine chloramine (TauCl) and taurine bromamine (TauBr). It has been demonstrated in vitro that TauCl exerts both antiinflammatory and anti-bacterial properties. Much less is known about TauBr. The present study was conducted to compare bactericidal and immunoregulatory capacity of TauBr with that of the major chlorinating oxidants: HOCl and TauCl. Moreover, the effect of nitrites and H(2)O(2) on TauBr activity was investigated.


METHODS
TauBr was prepared by reaction of HOBr with taurine. The reaction was monitored by UV absorption spectra.


METHODS
Bactericidal activity of TauBr, TauCl and HOCl was tested by incubation of E. coli with the compounds and determined by the pour-plate method. To test the anti-inflammatory activity the compounds were incubated with LPS and IFN-gamma stimulated murine peritoneal macrophages. The production of following mediators was measured: nitrites by Griess reaction; TNF-alpha, IL-6, IL-10, IL-12p40 using capture ELISA. In some experiments the compounds were incubated with either nitrites or H(2)O(2).


RESULTS
In our experimental set-up TauBr and HOCl exerted strong bactericidal effects on E. coli (MBC = 110 microM and 8 microM, respectively), while TauCl (< 1000 microM) did not kill test bacteria. However, both, TauBr and TauCl, at noncytotoxic concentrations (< 300 microM) inhibited the cytokine and nitric oxide production by macrophages. H(2)O(2) completely abolished the biological activities of TauBr but not those of TauCl. Nitrites did not affect any activity of TauBr or TauCl while they diminished the HOCl(-) mediated bacterial killing.


CONCLUSIONS
TauBr, despite very low concentration of Br(-) in body fluids, may support TauCl and HOCl in the regulation of inflammatory response and in killing of bacteria by neutrophils. However, TauBr activity in vivo will depend on the presence of H(2)O(2) and possible other mediators of inflammation which can compete with target molecules for TauBr.
Marcinkiewicz
J
J
Department of Immunology, Jagiellonian University Medical College, 18 Czysta St., 31-121, Craców, Poland. mmmarcin@cyf-kr.edu.pl
Mak
M
M
Bobek
M
M
Biedroń
R
R
Białecka
A
A
Koprowski
M
M
Kontny
E
E
Maśliński
W
W
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004347:Drug Interactions; D004355:Drug Stability; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009573:Nitrites / Q000737:chemistry / Q000494:pharmacology*; D013057:Spectrum Analysis; D013654:Taurine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D016207:Cytokines; D009573:Nitrites; D013654:Taurine; C052954:N-bromotaurine; D013656:Taurocholic Acid; D006861:Hydrogen Peroxide