Secretory phospholipase A2 group IIA (sPLA2-IIA) is an active participant of
inflammation. The
enzyme destroys bacterial cell wall and induces production of biologically active
lipid mediators. It is involved in various
pathological processes and high serum content and activity of sPLA2-IIA are associated with adverse cardiovascular events. Study of sPLA2-IIA regulation is of great physiological and clinical importance and is necessary for better understanding of mechanisms underlying
inflammation. Another major participant of inflammatory response is the
enzyme myeloperoxidase (MPO) which is secreted by neutrophils in the focus of
inflammation and catalyzes formation of HOCl and
HOBr. Both halogenated (chloro- and
bromohydrins) and oxidized
lipids are formed due to interaction between HOCl and
HOBr with unsaturated bonds of
phospholipid acyl chains. Previously we showed that oxidized
phospholipids stimulate sPLA2-IIA activity. In this study we examined the effects of chloro- and
bromohydrins of
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) on sPLA2-IIA activity. In contrast to POPC, chloro- and
bromohydrins of POPC (POPC-Cl and POPC-Br, respectively) were not hydrolyzed by sPLA2-IIA. In addition,
phospholipids which are sPLA2-IIA substrates, were not cleaved by the
enzyme in the presence of POPC-Cl and POPC-Br. Halogenohydrins of POPC prevented the activity of both purified and serum sPLA2-IIA. Blocking effects of POPC-Cl and POPC-Br were abolished by increased concentrations of
phospholipid-substrate. These results suggest that halogenated
phospholipids formed in MPO-dependent reactions can be considered as a new class of biologically active compounds potentially capable of regulating sPLA2-IIA activity in the areas of
inflammation and producing the effects opposite to those of oxidized
phospholipids. Control over sPLA2-IIA can be useful in the
therapy of diseases involving systemic
inflammation.