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Biomedical subjects

U Dippenaar

Publications and source records attributed to U Dippenaar.

4 recordsLinked to original sources
PubMed1987

Ascorbate and cysteine-mediated selective neutralisation of extracellular oxidants during N-formyl peptide activation of human phagocytes.

The effects of sodium ascorbate and cysteine (2.5 X 10(-5) M-2.5 X 10(-4) M) on the intensity and profile of luminol-enhanced chemiluminescence, superoxide generation, extracellular myeloperoxidase (MPO) activity and auto-iodination were measured in purified human polymorphonuclear leukocytes activated by the leukoattractant FMLP in vitro. Chemiluminescence studies were also performed using a whole-blood method. Cysteine (10(-4) M-2.5 X 10(-4) M) and ascorbate (2.5 X 10(-5) M-2.5 X 10(-4) M) caused significant inhibition of the early extracellular peak of FMLP-activated chemiluminescence and increased the intensity of the later occurring intracellular peak in both PMNL and blood. At the same concentrations both agents scavenged superoxide released by FMLP-activated PMNL, inhibited oxidant generation by extracellular MPO and decreased FMLP-induced auto-oxidation of PMNL. Administration of a single 1 gram oral dose of ascorbate to adult human volunteers was associated with significant reduction and enhancement respectively of the extracellular and intracellular luminol-enhanced chemiluminescence responses of FMLP-activated blood. These results show that the water soluble anti-oxidants cysteine and especially ascorbate selectively neutralise the reactivity of harmful reactive oxidants released by phagocytes, whilst the intracellular generation of antimicrobial oxidants remains intact.

Adult↗
PubMed1987

Dithranol mediates pro-oxidative inhibition of polymorphonuclear leukocyte migration and lymphocyte proliferation.

Dithranol (0.01-1 micrograms/ml), but not the auto-oxidized form, caused a dose-related enhancement of the generation of reactive oxidants by leukoattractant-activated polymorphonuclear leukocytes (PMNL) in vitro. At the same concentrations dithranol inhibited both PMNL migration to leukoattractants and mitogen-stimulated mononuclear leukocyte (MNL) proliferation. Catalase (50-100 units/ml) protected both PMNL migration and MNL proliferation from dithranol whilst ascorbate and cysteine (1 mM), which maintain dithranol in the biologically active reduced state, potentiated the inhibition. To establish the molecular mechanism of the pro-oxidative activity of dithranol its effects on cytosolic protein kinase C (PKC) activity were investigated. Dithranol caused a dose-related activation of PKC by apparent substitution for 1,2-diolein. These results demonstrate that dithranol, but not its auto-oxidation products, activates PKC which in turn initiates the generation of reactive oxidants by PMNL. Since reactive oxidants are immunosuppressive the therapeutic mechanisms of dithranol may be related to pro-oxidative interactions of this agent with skin phagocytes.

Adult↗
PubMed1986

Clofazimine-mediated regulation of human polymorphonuclear leukocyte migration by pro-oxidative inactivation of both leukoattractants and cellular migratory responsiveness.

The effects of clofazimine (0.15-20 micrograms/ml) on the spontaneous and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-stimulated migration, membrane-associated oxidative metabolism, degranulation and production of prostaglandin (PG) E2 by human polymorphonuclear in vitro have been investigated. Clofazimine at concentrations of 0.3 microgram/ml and greater significantly increased both the spontaneous and FMLP-stimulated chemiluminescence (CL), hexose monophosphate shunt (HMS) activity, myeloperoxidase-mediated protein iodination, auto-iodination, degranulation and PGE2 production by PMNL. At the same concentrations clofazimine inhibited both random and leukoattractant-induced migration of PMNL. Inhibition of PMNL migration by clofazimine was due to both a cell-directed auto-oxidative mechanism and by functional inactivation of FMLP. Clofazimine mediated inhibition of PMNL migration was prevented by the anti-oxidants cysteine and dapsone but not by the potent inhibitors of PG synthetase indomethacin and piroxicam. Anti-oxidants also protected FMLP from functional inactivation by clofazimine-exposed PMNL. Clofazimine increased both the spontaneous and FMLP-stimulated production of PGE2 by PMNL from four children with chronic granulomatous disease (CGD). Clofazimine is not an oxidising agent nor did it stimulate membrane-associated oxidative metabolism in CGD or NaF-pulsed normal PMNL. These data show that clofazimine-mediated inhibition of PMNL migration is dependent on intact cellular membrane-associated oxidative metabolism. Clofazimine is therefore a pro-oxidative anti-inflammatory agent.

Adult↗