TY - JOUR
KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
KW - Acetophenones
KW - Arachidonic Acid
KW - Arachidonic Acids
KW - Clofazimine
KW - Dose-Response Relationship, Drug
KW - Humans
KW - In Vitro Techniques
KW - Isoquinolines
KW - N-Formylmethionine Leucyl-Phenylalanine
KW - Neutrophils
KW - Phospholipases
KW - Phospholipases A
KW - Phospholipases A2
KW - Piperazines
KW - Protein Kinase C
KW - Superoxides
AU - Anderson R
AU - Beyers A D
AU - Savage J E
AU - Nel A E
AB - <p>The anti-leprosy agent, clofazimine, at concentrations of 0.1-5 micrograms/ml caused a dose-related, stimulus-non-specific (N-formyl-methionyl-leucyl-phenylalanine, calcium ionophore, opsonised zymosan, arachidonic acid and phorbol myristate acetate) potentiation of superoxide generation by human neutrophils in vitro without affecting basal oxidative responses. The pro-oxidative interactions of clofazimine with neutrophils were eliminated by the phospholipase A2 inhibitor 4-p-bromophenacyl bromide but not by the protein kinase C (PKC) inhibitor H-7. In support of these observations clofazimine promoted the release of radiolabeled arachidonic acid from neutrophil membrane phospholipids but did not influence the activity of PKC in cytosolic extracts of neutrophils or of purified PKC from rat brain. Pro-oxidative interactions of clofazimine with human phagocytes may contribute to the intraphagocytic antimycobacterial activity of this agent.</p>
BT - Biochemical pharmacology
C1 - http://www.ncbi.nlm.nih.gov/pubmed/2849452?dopt=Abstract
DA - 1988 Dec 15
DO - 10.1016/0006-2952(88)90332-2
IS - 24
J2 - Biochem. Pharmacol.
LA - eng
N2 - <p>The anti-leprosy agent, clofazimine, at concentrations of 0.1-5 micrograms/ml caused a dose-related, stimulus-non-specific (N-formyl-methionyl-leucyl-phenylalanine, calcium ionophore, opsonised zymosan, arachidonic acid and phorbol myristate acetate) potentiation of superoxide generation by human neutrophils in vitro without affecting basal oxidative responses. The pro-oxidative interactions of clofazimine with neutrophils were eliminated by the phospholipase A2 inhibitor 4-p-bromophenacyl bromide but not by the protein kinase C (PKC) inhibitor H-7. In support of these observations clofazimine promoted the release of radiolabeled arachidonic acid from neutrophil membrane phospholipids but did not influence the activity of PKC in cytosolic extracts of neutrophils or of purified PKC from rat brain. Pro-oxidative interactions of clofazimine with human phagocytes may contribute to the intraphagocytic antimycobacterial activity of this agent.</p>
PY - 1988
SP - 4635
EP - 41
T2 - Biochemical pharmacology
TI - Apparent involvement of phospholipase A2, but not protein kinase C, in the pro-oxidative interactions of clofazimine with human phagocytes.
VL - 37
SN - 0006-2952
ER -