An in vitro comparison of the effects of the prooxidative riminophenazines clofazimine and B669 on neutrophil phospholipase A2 activity and superoxide generation.
The effects of the antimycobacterial agent clofazimine and its experimental analogue B669 on the phospholipase A2 activity of and superoxide generation by human blood neutrophils were investigated in vitro. Coincubation of neutrophils with clofazimine or B669 (1-10 micrograms/mL) was accompanied by a dose-related increase in the release of both [3H]lysophosphatidylcholine (LPC) and [3H]arachidonate (AA). Both agents (1 microgram/mL) also increased the production of superoxide by resting and FMLP-stimulated neutrophils. Addition of reagent AA and especially LPC to neutrophils mimicked the effects of the riminophenazines, while alpha-tocopherol, a lysophospholipid complex-forming agent, neutralized the prooxidative interactions of clofazimine and B669 with these cells. These observations demonstrate that LPC, and to a lesser extent AA, generated during exposure of human neutrophils to clofazimine or B669 are the primary mediators of the prooxidative interactions of these riminophenazines with phagocytes.
Department of Hematology, Medical University of Southern Africa, Medunsa.
M M
MM
Krajewska
R
R
Anderson
D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism; D002991:Clofazimine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010741:Phospholipases A / Q000187:drug effects / Q000378:metabolism*; D054467:Phospholipases A2; D013481:Superoxides / Q000378:metabolism*
D000890:Anti-Infective Agents; D001095:Arachidonic Acids; D008070:Lipopolysaccharides; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C030428:B 669; D002991:Clofazimine; D010741:Phospholipases A; D054467:Phospholipases A2