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Titolo:
ATP-mediated killing of intracellular mycobacteria by macrophages is a P2X(7)-dependent process inducing bacterial death by phagosome-lysosome fusion
Autore:
Fairbairn, IP; Stober, CB; Kumararatne, DS; Lammas, DA;
Indirizzi:
Univ Birmingham, Med Sch Birmingham, MRC, Ctr Immune Regulat, Birmingham B15 2TT, W Midlands, England Univ Birmingham Birmingham W Midlands England B15 2TT W Midlands, England
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 6, volume: 167, anno: 2001,
pagine: 3300 - 3307
SICI:
0022-1767(20010915)167:6<3300:AKOIMB>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; PHOSPHOLIPASE A(2) ACTIVITY; BACILLE CALMETTE-GUERIN; NATURAL-RESISTANCE; PHOSPHATIDIC-ACID; ENDOSOME FUSION; FACTOR-ALPHA; NRAMP1 GENE; TUBERCULOSIS; INFECTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Fairbairn, IP Univ Birmingham, Med Sch Birmingham, MRC, Ctr Immune Regulat, Birmingham B15 2TT, W Midlands, England Univ Birmingham Birmingham W Midlands England B15 2TT gland
Citazione:
I.P. Fairbairn et al., "ATP-mediated killing of intracellular mycobacteria by macrophages is a P2X(7)-dependent process inducing bacterial death by phagosome-lysosome fusion", J IMMUNOL, 167(6), 2001, pp. 3300-3307

Abstract

Mycobacterium tuberculosis survives within host macrophages by actively inhibiting phagosome fusion with lysosomes. Treatment of infected macrophageswith ATP induces both cell apoptosis and rapid killing of intracellular mycobacteria. The following studies were undertaken to characterize the effector pathway(s) involved. Macrophages were obtained from p47(phox) and inducible NO synthase gene-disrupted mice (which are unable to produce reactive oxygen and nitrogen radicals, respectively) and P2X(7) gene-disrupted mice. RAW murine macrophages transfected with either the natural resistance-associated macrophage protein gene 1 (Nramp1)-resistant or Nramp1-susceptible gene were also used. The cells were infected with bacille Calmette-Guerin (BCG), and intracellular mycobacterial trafficking was analyzed using confocal and electron microscopy. P2X(7) receptor activation was essential for effective ATP-induced mycobacterial killing, as its bactericidal activity was radically diminished in P2X(7)(-/-) macrophages. ATP-mediated killing of BCG within p47(phox-/-), inducible NO synthase(-/-), and Nramp(s) cells was unaffected, demonstrating that none of these mechanisms have a role in the ATP/P2X(7) effector pathway. Following ATP stimulation, BCG-containing phagosomes rapidly coalesce and fuse with lysosomes. Blocking of macrophage phospholipase D activity with butan-1-ol blocked BCG killing, but not macrophage death. ATP stimulates phagosome-lysosome fusion with concomitant mycobacterial death via P2X(7) receptor activation. Macrophage death and mycobacterial killing induced by the ATP/P2X(7) signaling pathway can be uncoupled, and diverge proximal to phospholipase D activation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 16:45:52