Effect of chloroquine on phagolysosomal fusion in cultured guinea pig alveolar macrophages: Implications in drug delivery

Abstract

The aim of this study was to evaluate the effects of chloroquine on phagolysosomal fusion (PLF) in cultured guinea pig alveolar macrophages (AMs). This technique may be of significance for antitubercular drugs, because.the survival of Mycobacterium tuberculosis is linked to evasion of PLF. Guinea pig AMs were obtained from anesthetized animals after exsanguination. The AMs were cultured at a density of 1 x 10 6 cell/mL in 24-well plates after attachment to 13-mm coverslips. Culture conditions were at 37 o C, with 95% air/5% C O2

Killing of Escherichia coli by Crohnʼs Disease Monocyte-derived Macrophages and Its Enhancement by Hydroxychloroquine and Vitamin D

“… 59 This effect is dose-dependent, however, and it has been reported that chloroquine may even enhance fusion at lower concentrations. 60 In support of this, it has been shown to inhibit intramacrophage replication of Mycobacterium tuberculosis and to enhance the antituberculosis protectiveness of both isoniazid and 25 OH-vitamin D 3 . 61 Moreover CD-derived AIEC can replicate within phagolysosomes, having escaped autophagy, 9 whereas rapamycin, which stimulates autophagy, becomes ineffective once intramacrophage replication of AIEC has become established.…”

Phagocytosis of melanized Aspergillus conidia by macrophages exerts cytoprotective effects by sustained PI3K/Akt signalling

“…(2002) demonstrated that phagolysosome formation was significantly reduced for pigmented wild‐type conidia compared with white pksP mutant conidia, which apparently resulted in a reduced killing rate of wild‐type conidia. To investigate whether the decreased rate of formation of functional phagolysosomes is associated with the anti‐apoptotic property of wild‐type conidia, we investigated the effect of chloroquine, a known enhancer of phagolysosome acidification when applied in low concentrations (Hart et al ., 1987; Collins et al ., 1997; Bhat and Hickey, 2000), on STS‐induced caspase‐3 processing in infected macrophages. To assess the transfer of ingested conidia into an acidic environment in the absence or presence of chloroquine, MH‐S cells were stained with LysoTracker Red DND‐99 (Via et al ., 1998) for 2 h before being exposed to wild‐type or pksP mutant conidia.…”

Hyperspectral Imaging Using Intracellular Spies: Quantitative Real-Time Measurement of Intracellular Parameters In Vivo during Interaction of the Pathogenic Fungus Aspergillus fumigatus with Human Monocytes

“…fumigatus can restrict the formation of phagolysosomes if it is successfully localised to the compartment [ 46 ]. Regarding the ability of chloroquine to stimulate phagosome and lysosome fusion [ 61 ], the acidified environment in the phagolysosome was maintained as it happened in the presence of pksP [ 51 ]. To examine the impact of melanin on the acidic environment in light of its anti-apoptotic properties, apoptotic cells were exposed to chloroquine.…”

“…phagosome and lysosome). It increases enzyme activities in these organelles and reduces the pH by increasing the reactive oxygen species [ 61 , 67 ]. We observed that when an apoptotic monocyte is exposed to chloroquine, infection with either wild-type or melanin free A .…”