| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Medical Research Council Center for Immune Regulation, Division of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom; and
Division of Medicine, University of Bristol, Bristol, United Kingdom
We previously demonstrated that extracellular ATP stimulated macrophage death and mycobacterial killing within Mycobacterium bovis Bacille Calmette-Guérin (BCG)-infected human macrophages. ATP increases the cytosolic Ca2+ concentration in macrophages by mobilizing intracellular Ca2+ via G protein-coupled P2Y receptors, or promoting the influx of extracellular Ca2+ via P2X purinoceptors. The relative contribution of these receptors and Ca2+ sources to ATP-stimulated macrophage death and mycobacterial killing was investigated. We demonstrate that 1) ATP mobilizes Ca2+ in UTP-desensitized macrophages (in Ca2+-free medium) and 2) UTP but not ATP fails to deplete the intracellular Ca2+ store, suggesting that the pharmacological properties of ATP and UTP differ, and that a Ca2+-mobilizing P2Y purinoceptor in addition to the P2Y2 subtype is expressed on human macrophages. ATP and the Ca2+ ionophore, ionomycin, promoted macrophage death and BCG killing, but ionomycin-mediated macrophage death was inhibited whereas BCG killing was largely retained in Ca2+-free medium. Pretreatment of cells with thapsigargin (which depletes inositol (1,4,5)-trisphosphate-mobilizable intracellular stores) or 1,2-bis-(2-aminophenoxy)ethane-N, N, N',N'-tetraacetic acid acetoxymethyl ester (an intracellular Ca2+ chelator) failed to inhibit ATP-stimulated macrophage death but blocked mycobacterial killing. Using the acidotropic molecular probe, 3-(2,4-dinitroanilino)-3'-amino-N-methyl dipropylamine, it was revealed that ATP stimulation promoted the acidification of BCG-containing phagosomes within human macrophages, and this effect was similarly dependent upon Ca2+ mobilization from intracellular stores. We conclude that the cytotoxic and bactericidal effects of ATP can be uncoupled and that BCG killing is not the inevitable consequence of death of the host macrophage.
This article has been cited by other articles:
|
|
 |
|
  N. R. Patel, K. Swan, X. Li, S. D. Tachado, and H. Koziel Impaired M. tuberculosis-mediated apoptosis in alveolar macrophages from HIV+ persons: potential role of IL-10 and BCL-3 J. Leukoc. Biol., July 1, 2009; 86(1): 53 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. R. Patel, J. Zhu, S. D. Tachado, J. Zhang, Z. Wan, J. Saukkonen, and H. Koziel HIV Impairs TNF-{alpha} Mediated Macrophage Apoptotic Response to Mycobacterium tuberculosis J. Immunol., November 15, 2007; 179(10): 6973 - 6980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Soualhine, A.-E. Deghmane, J. Sun, K. Mak, A. Talal, Y. Av-Gay, and Z. Hmama Mycobacterium bovis Bacillus Calmette-Guerin Secreting Active Cathepsin S Stimulates Expression of Mature MHC Class II Molecules and Antigen Presentation in Human Macrophages J. Immunol., October 15, 2007; 179(8): 5137 - 5145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-R. Woo, R. G. Barletta, and C. J. Czuprynski Extracellular ATP Is Cytotoxic to Mononuclear Phagocytes but Does Not Induce Killing of Intracellular Mycobacterium avium subsp. paratuberculosis Clin. Vaccine Immunol., September 1, 2007; 14(9): 1078 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. de Jonge, G. Pehau-Arnaudet, M. M. Fretz, F. Romain, D. Bottai, P. Brodin, N. Honore, G. Marchal, W. Jiskoot, P. England, et al. ESAT-6 from Mycobacterium tuberculosis Dissociates from Its Putative Chaperone CFP-10 under Acidic Conditions and Exhibits Membrane-Lysing Activity J. Bacteriol., August 15, 2007; 189(16): 6028 - 6034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Fernando, B. M. Saunders, R. Sluyter, K. K. Skarratt, H. Goldberg, G. B. Marks, J. S. Wiley, and W. J. Britton A Polymorphism in the P2X7 Gene Increases Susceptibility to Extrapulmonary Tuberculosis Am. J. Respir. Crit. Care Med., February 15, 2007; 175(4): 360 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sinha, A. Singh, V. Satchidanandam, and K. Natarajan Impaired Generation of Reactive Oxygen Species during Differentiation of Dendritic Cells (DCs) by Mycobacterium tuberculosis Secretory Antigen (MTSA) and Subsequent Activation of MTSA-DCs by Mycobacteria Results in Increased Intracellular Survival J. Immunol., July 1, 2006; 177(1): 468 - 478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Burnstock Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol. Rev., March 1, 2006; 58(1): 58 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tomioka, C. Sano, K. Sato, K. Ogasawara, T. Akaki, K. Sano, S. S. Cai, and T. Shimizu Combined Effects of ATP on the Therapeutic Efficacy of Antimicrobial Drug Regimens against Mycobacterium avium Complex Infection in Mice and Roles of Cytosolic Phospholipase A2-Dependent Mechanisms in the ATP-Mediated Potentiation of Antimycobacterial Host Resistance J. Immunol., November 15, 2005; 175(10): 6741 - 6749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Myers, B. Eilertson, S. A. Fulton, J. L. Flynn, and D. H. Canaday The Purinergic P2X7 Receptor Is Not Required for Control of Pulmonary Mycobacterium tuberculosis Infection Infect. Immun., May 1, 2005; 73(5): 3192 - 3195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. F. Pais and R. Appelberg Induction of Mycobacterium avium growth restriction and inhibition of phagosome-endosome interactions during macrophage activation and apoptosis induction by picolinic acid plus IFN{gamma} Microbiology, May 1, 2004; 150(5): 1507 - 1518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Saunders, S. L. Fernando, R. Sluyter, W. J. Britton, and J. S. Wiley A Loss-of-Function Polymorphism in the Human P2X7 Receptor Abolishes ATP-Mediated Killing of Mycobacteria J. Immunol., November 15, 2003; 171(10): 5442 - 5446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Villarreal-Ramos, M. McAulay, V. Chance, M. Martin, J. Morgan, and C. J. Howard Investigation of the Role of CD8+ T Cells in Bovine Tuberculosis In Vivo Infect. Immun., August 1, 2003; 71(8): 4297 - 4303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Sly, S. M. Hingley-Wilson, N. E. Reiner, and W. R. McMaster Survival of Mycobacterium tuberculosis in Host Macrophages Involves Resistance to Apoptosis Dependent upon Induction of Antiapoptotic Bcl-2 Family Member Mcl-1 J. Immunol., January 1, 2003; 170(1): 430 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Canaday, R. Beigi, R. F. Silver, C. V. Harding, W. H. Boom, and G. R. Dubyak ATP and Control of Intracellular Growth of Mycobacteria by T Cells Infect. Immun., November 1, 2002; 70(11): 6456 - 6459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. P. Fairbairn, C. B. Stober, D. S. Kumararatne, and D. A. Lammas ATP-Mediated Killing of Intracellular Mycobacteria by Macrophages Is a P2X7-Dependent Process Inducing Bacterial Death by Phagosome-Lysosome Fusion J. Immunol., September 15, 2001; 167(6): 3300 - 3307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Kusner and J. A. Barton ATP Stimulates Human Macrophages to Kill Intracellular Virulent Mycobacterium tuberculosis Via Calcium-Dependent Phagosome-Lysosome Fusion J. Immunol., September 15, 2001; 167(6): 3308 - 3315. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
