       Document 0707
 DOCN  M9640707
 TI    H2O2 induces monocyte apoptosis and reduces viability of Mycobacterium
       avium-M. intracellulare within cultured human monocytes.
 DT    9604
 AU    Laochumroonvorapong P; Paul S; Elkon KB; Kaplan G; Laboratory of
       Cellular Physiology and Immunology, Rockefeller; University, New York,
       New York, USA.
 SO    Infect Immun. 1996 Feb;64(2):452-9. Unique Identifier : AIDSLINE
       MED/96145063
 AB    Mycobacterium avium-M. intracellulare, an intracellular parasite of
       mononuclear phagocytes, rarely causes disease in immunocompetent
       individuals. In contrast, in human immunodeficiency virus type
       1-infected patients, M. avium-M. intracellulare can infect almost every
       tissue and organ. This suggests that immunocompetent individuals have a
       protective mechanism to control or prevent the infection. How
       mycobacterial may be killed by the host immune response is unclear. We
       have recently reported that induction of apoptosis of Mycobacterium
       bovis BCG-infected macrophages with ATP4- was associated with killing of
       the intracellular mycobacteria. In the present study, a long-term
       culture of M. avium-M. intracellulare-infected monocytes was used to
       further evaluate the interaction between M. avium-M. intracellulare and
       primary human monocytes. In our system, M. avium-M. intracellulare
       parasitized the human monocytes and appeared to replicate slowly over 14
       days within the host cells. To examine the role of apoptotic mechanisms
       in survival or death of intracellular mycobacteria, M. avium-M.
       intracellulare-infected human monocytes were treated with a monoclonal
       antibody to Fas receptor (APO-1/CD95) or with various concentrations of
       H2O2. Although both of these exogenous agents induced monocyte
       apoptosis, optimal killing (65% reduction in CFU) of intracellular M.
       avium-M. intracellulare was observed only when M. avium-M.
       intracellulare-infected cells were treated with 10 mM H2O2. Fas-induced
       apoptosis did not affect M. avium-M. intracellulare viability. Our
       results suggest that not all stimuli of monocyte apoptosis induce
       killing of intracellular M. avium-M. intracellulare. Since release of
       H2O2 following phagocytosis of mycobacteria has been documented,
       H2O2-induced apoptotic death of M. avium-M. intracellulare-infected
       monocytes and its association with killing of the intracellular bacilli
       may be a physiological mechanism of host defense against M. avium-M.
       intracellulare.
 DE    Acquired Immunodeficiency Syndrome/IMMUNOLOGY  Antigens, CD95/PHYSIOLOGY
       Apoptosis/*DRUG EFFECTS  Cells, Cultured  Cycloheximide/PHARMACOLOGY
       DNA/METABOLISM  Human  Hydrogen Peroxide/*PHARMACOLOGY  Monocytes/*DRUG
       EFFECTS/MICROBIOLOGY  Mycobacterium avium Complex/*DRUG EFFECTS/GROWTH &
       DEVELOPMENT/  IMMUNOLOGY  Mycobacterium avium-intracellulare
       Infection/IMMUNOLOGY  Nitric Oxide/PHYSIOLOGY  Support, U.S. Gov't,
       P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

