RESUMO
We describe a case of known lung malignancy presenting acutely with bronchial obstruction. A piece of tumor from the left main bronchus (occluded by primary tumor) had been aspirated into the previously patent right main bronchus, leading to acute respiratory distress. The obstruction was cleared before intervention by expectoration.
Assuntos
Neoplasias Brônquicas/diagnóstico , Dispneia/etiologia , Pneumopatias Obstrutivas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Sons Respiratórios/etiologia , Neoplasias Brônquicas/fisiopatologia , Broncoscopia , Dispneia/fisiopatologia , Humanos , Pneumopatias Obstrutivas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Sons Respiratórios/fisiopatologia , Tomografia Computadorizada por Raios XRESUMO
Macrophage apoptosis occurs within the granuloma, which is essential for successful immunity to tuberculosis. In vitro macrophage apoptosis is associated with the killing of intracellular Mycobacterium tuberculosis. A greater understanding of these observations will lead to new immunotherapies and improved vaccine design. The relevant apoptotic stimuli, the anti-mycobacterial mechanisms that they stimulate and their physiological relevance are reviewed in this paper.
Assuntos
Apoptose , Macrófagos/microbiologia , Macrófagos/patologia , Infecções por Mycobacterium/metabolismo , Animais , Granuloma/microbiologia , Granuloma/patologia , Humanos , Imunidade , Mycobacterium tuberculosis/metabolismoRESUMO
Mycobacterium tuberculosis survives within host macrophages by actively inhibiting phagosome fusion with lysosomes. Treatment of infected macrophages with 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-Guérin (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.