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Titolo:
ATP-mediated killing of Mycobacterium bovis Bacille Calmette-Guerin withinhuman macrophages is calcium dependent and associated with the acidification of mycobacteria-containing phagosomes
Autore:
Stober, CB; Lammas, DA; Li, CM; Kumararatne, DS; Lightman, SL; McArdle, CA;
Indirizzi:
Univ Birmingham, Sch Med, Div Immun & Infect, MRC,Ctr Immune Regulat, Birmingham B15 2TT, W Midlands, England Univ Birmingham Birmingham W Midlands England B15 2TT W Midlands, England Univ Bristol, Div Med, Bristol, Avon, England Univ Bristol Bristol Avon England istol, Div Med, Bristol, Avon, England
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 10, volume: 166, anno: 2001,
pagine: 6276 - 6286
SICI:
0022-1767(20010515)166:10<6276:AKOMBB>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
PURINERGIC P-2Z RECEPTOR; PHOSPHOLIPASE-D; NUCLEOTIDE RECEPTOR; EXTRACELLULAR ATP; MURINE MACROPHAGES; INTRACELLULAR CA2+; EPITHELIAL-CELLS; PLASMA-MEMBRANE; LYSOSOME FUSION; TUBERCULOSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
60
Recensione:
Indirizzi per estratti:
Indirizzo: Lammas, DA Univ Birmingham, Sch Med, Div Immun & Infect, MRC,Ctr Immune Regulat, Birmingham B15 2TT, W Midlands, England Univ Birmingham Birmingham W Midlands England B15 2TT England
Citazione:
C.B. Stober et al., "ATP-mediated killing of Mycobacterium bovis Bacille Calmette-Guerin withinhuman macrophages is calcium dependent and associated with the acidification of mycobacteria-containing phagosomes", J IMMUNOL, 166(10), 2001, pp. 6276-6286

Abstract

We previously demonstrated that extracellular ATP stimulated macrophage death and mycobacterial killing within :Mycobacterium bovis Bacille Calmette-Guerin (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 P2Y(2) 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 16:12:49