After phagocytosis, the intracellular pathogen Mycobacterium tuberculosis arrests the progression of the nascent phagosome into a phagolysosome, allowing for replication in a compartment that resembles early endosomes. To better understand the molecular mechanisms that govern phagosome maturation arrest, we performed a visual screen on a set of M. tuberculosis mutants specifically attenuated fo...

We studied phagolysosomal pH in rabbit alveolar macrophages (AM) incubated with 0-15 microM chloroquine. There was a dose-related increase in pH with chloroquine concentration. Electron microscopy showed that chloroquine increased lysosomal size. In a second experiment we studied dissolution of radiolabeled cobalt oxide particles by rabbit AM, phagolysosomal pH, and lysosomal size. The cells we...

Myeloperoxidase (MPO), hemoprotein present in neutrophils and monocytes, has an essential role in immune surveillance and host defense mechanisms. Upon phagocyte activation in peripheral tissues and fluids, MPO is secreted into both the extracellular milieu and the phagolysosome where it uses hydrogen peroxide (H2O2) generated during a respiratory burst by activated NADPH as co-substrate. (Hurs...

Amyloid β (Aβ) peptide, a causative agent of Alzheimer's disease, forms two types of aggregates: oligomers and fibrils. These aggregates induce inflammatory responses, such as interleukin-1β (IL-1β) production by microglia, which are macrophage-like cells located in the brain. In this study, we examined the effect of the two forms of Aβ aggregates on IL-1β production in mouse primary microglia....

Neutrophils and macrophages engulf not only microorganisms but also damaged tissue and degrade these materials in the phagolysosome (1-5). In wound healing, early infiltration of neutrophils followed by macrophage infiltration are important defense mechanisms for repair of tissue damage. Infiltrating neutrophils clear the wounded area of foreign particles and bacteria and are then extruded with...

Phagosomes are key organelles for the innate ability of macrophages to participate in tissue remodeling, clear apoptotic cells, and restrict the spread of intracellular pathogens. To understand the functions of phagosomes, we initiated the systematic identification of their proteins. Using a proteomic approach, we identified . 140 proteins associated with latex bead– containing phagosomes. Amon...

Coxiella burnetii is a gram-variable obligate intracellular bacterium which carries out its development cycle in the phagolysosome of eucaryotic cells. Ultrastructural analysis of C. burnetii, in situ and after Renografin purification, by transmission electron microscopy of lead-stained thin sections has revealed extreme pleomorphism as demonstrated by two morphological cell types, a large cell...

Apoptotic cells in animals are engulfed by phagocytic cells and subsequently degraded inside phagosomes. To study the mechanisms controlling the degradation of apoptotic cells, we developed time-lapse imaging protocols in developing Caenorhabditis elegans embryos and established the temporal order of multiple events during engulfment and phagosome maturation. These include sequential enrichment...

Rhodococcus equi is an intracellular pathogen which causes pneumonia in young horses and in immunocompromised humans. R. equi arrests phagosome maturation in macrophages at a prephagolysosome stage and grows inside a privileged compartment. Here, we show that, in murine macrophages activated with gamma interferon and lipopolysaccharide, R. equi does not multiply but stays viable for at least 24...

Korean red ginseng (KRG) has long been used in traditional Korean and Oriental medicine. However, the anti-bacterial mechanism and therapeutic efficiency of KGR for intracellular Brucella infection are still unclear. In this study, the bactericidal activity of Korean red ginseng acidic polysaccharide (RGAP) on Brucella (B.) abortus and its cytotoxic effects on RAW 264.7 cells were evaluated. In...