The pro-oxidative riminophenazine B669 neutralizes the inhibitory effects of Mycobacterium tuberculosis on phagocyte antimicrobial activity.
The effects of clofazimine, a riminophenazine antimicrobial agent, and its analogue B669 on phagocyte functions have been investigated. Clofazimine, at concentrations attainable in vivo, and B669, in particular, increased the intracellular killing ability of phagocytes following appropriate cell stimulation. Similarly, nitro blue tetrazolium reduction, hydrogen peroxide production, lysosyme release and hexose monophosphate shunt activity were all increased by treating phagocytes with the riminophenazines. It has previously been shown that a 25 kDa glycolipoprotein derived from Mycobacterium tuberculosis inhibits phagocyte functions associated with phagocyte antimicrobial activity. The present study confirms these observations. A further aspect of the study examined the ability of riminophenazines to reverse the inhibition of phagocyte functions by the 25 kDa mycobacterial fraction. Whilst both riminophenazines were capable of partially but significantly reversing the inhibition due to the mycobacterial fraction, the restorative capacity of B669 was greater than that of clofazimine.
Wadee
A A
AA
Department of Immunology, University of Witwatersrand, Johannesburg, South Africa.
Kuschke
R H
RH
Dooms
T G
TG
Anderson
R
R
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000633:toxicity*; D002991:Clofazimine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D016897:Respiratory Burst / Q000187:drug effects
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C030428:B 669; D002991:Clofazimine