EPO (
eosinophil peroxidase) and MPO (
myeloperoxidase) are highly basic
haem enzymes that can catalyse the production of
HOBr (
hypobromous acid). They are released extracellularly by activated leucocytes and their binding to the polyanionic glycosa-minoglycan components of extracellular matrix (
proteoglycans and
hyaluronan) may localize the production of
HOBr to these materials. It is shown in the present paper that the reaction of
HOBr with
glycosaminoglycans (
heparan sulfate,
heparin,
chondroitin sulfate and
hyaluronan) generates
polymer-derived N-bromo derivatives (bromamines, dibromamines, N-bromosulfon-
amides and bromamides). Decomposition of these species, which can occur spontaneously and/or via one-electron reduction by low-valent transition
metal ions (Cu+ and Fe2+), results in
polymer fragmentation and modification. One-electron reduction of the N-bromo derivatives generates radicals that have been detected by EPR spin trapping. The species detected are consistent with
metal ion-dependent
polymer fragmentation and modification being initiated by the formation of
nitrogen-centred (aminyl, N-bromoaminyl, sulfonamidyl and amidyl) radicals. Previous studies have shown that the reaction of
HOBr with
proteins generates N-bromo derivatives and results in fragmentation of the
polypeptide backbone. The reaction of
HOBr with extracellular matrix synthesized by smooth muscle cells in vitro induces the release of
carbohydrate and
protein components in a time-dependent manner, which is consistent with fragmentation of these materials via the formation of N-bromo derivatives. The degradation of extracellular matrix
glycosaminoglycans and
proteins by
HOBr may contribute to tissue damage associated with inflammatory diseases such as
asthma.