Vol.55 No.5 September 2007
Relationship between the picolinic acid-induced potentiation of macrophage antimycobacterial activity and macrophage apoptosis
Department of Microbiology and Immunology, Shimane University School of Medicine, Enya-cho 89-1, Izumo, Shimane, Japan
Abstract
It has been reported that picolinic acid (PA) potentiated the antimicrobial activity of mouse bone marrow-derived macrophages (MΦs) against intracellular Mycobacterium avium complex (MAC) and that such PA effects were accompanied by PA-induced MΦ apoptosis. It is of interest to examine whether or not such a phenomenon is also observed for human MΦs. In the present study, we examined PA activity in inducing apoptosis of THP-1 human MΦs (THP-1 MΦs) using the Annexin V and DNA laddering assay methods. Flow cytometric studies on test MΦs stained with Annexin V demonstrated that PA treatment induced phosphatidylserine translocation to the outer leaflet of the cell membrane THP-1 MΦs with or without M. avium infection. On the other hand, PA treatment did not cause significant levels of DNA laddering, even when test THP-1 MΦs were infected with M. avium. These findings suggest that PA may induce the early phase apoptotic events in THP-1 MΦs, without inducing DNA fragmentation characteristic to the middle to late phase apoptosis. Our present results provide insights into the possible role of MΦ apoptosis in the PA-induced potentiation of MΦ anti-MAC anitmicrobial activity.
Key word
picolinic acid, macrophage, apoptosis, bactericidal activity, Mycobacterium avium
Received
September 6, 2006
Accepted
May 29, 2007
Jpn. J. Chemother. 55 (5): 358-362, 2007
