Matrix metalloproteinases (MMP) can activate cytokines or destroy tight junctions, thus playing a crucial role in main features of human cerebral malaria (CM): inflammation, blood brain barrier (BBB) damage, and hypoxia. Here, we studied the effects of oxygen-loaded nanobubbles (OLN) on hypoxia-dependent regulation of gelatinases (MMP-2 and MMP-9) in haemozoin(HZ)-fed human monocytes. Cells secreted basal levels of MMP-9 but not of MMP-2. Hypoxia reduced basal MMP-9 release without affecting expression. HZ and its lipoperoxidation derivative 15-HETE enhanced MMP-9 expression and release, either in normoxia or hypoxia. OLN, constituted by dextran shell and oxygen-storing decafluoropentane core, with sizes of about 500 nm and a negative surface charge, showed good capacity of O2 delivery, not accompanied by O3 generation after UV rays (346 nm) sterilization, and not displaying toxic effects on cells. OLN abrogated both hypoxia-dependent reduction or HZ-dependent increase of MMP-9 secretion. These data suggest that OLN may prevent MMP-dependent inflammation and BBB damage in CM, thus potentially being a promising candidate for adjuvant therapy in complicated malaria.
Effects of oxygen-loaded dextran nanobubbles on regulation of gelatinases in haemozoin-fed human monocytes
PRATO, Mauro;POLIMENI, Manuela;VALENTE, Elena;NOVELLO, Matteo;GIRIBALDI, Giuliana;GUIOT, Caterina
2012-01-01
Abstract
Matrix metalloproteinases (MMP) can activate cytokines or destroy tight junctions, thus playing a crucial role in main features of human cerebral malaria (CM): inflammation, blood brain barrier (BBB) damage, and hypoxia. Here, we studied the effects of oxygen-loaded nanobubbles (OLN) on hypoxia-dependent regulation of gelatinases (MMP-2 and MMP-9) in haemozoin(HZ)-fed human monocytes. Cells secreted basal levels of MMP-9 but not of MMP-2. Hypoxia reduced basal MMP-9 release without affecting expression. HZ and its lipoperoxidation derivative 15-HETE enhanced MMP-9 expression and release, either in normoxia or hypoxia. OLN, constituted by dextran shell and oxygen-storing decafluoropentane core, with sizes of about 500 nm and a negative surface charge, showed good capacity of O2 delivery, not accompanied by O3 generation after UV rays (346 nm) sterilization, and not displaying toxic effects on cells. OLN abrogated both hypoxia-dependent reduction or HZ-dependent increase of MMP-9 secretion. These data suggest that OLN may prevent MMP-dependent inflammation and BBB damage in CM, thus potentially being a promising candidate for adjuvant therapy in complicated malaria.
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