Author: Vojo Deretic; Graham S Timmins
Title: Azithromycin and ciprofloxacin have a chloroquine-like effect on respiratory epithelial cells Document date: 2020_3_31
ID: i4ijuk36_5
Snippet: Azithromycin corrects organellar pH in CF lung epithelial cells. We tested the effects of AZT on CF respiratory epithelial cells in the absence of bacteria or microbial innate immunity agonists. Among the tests employed, we examine the pH of intracellular organelles since prior studies [27] [28] [29] [32] [33] [34] [35] have indicated that these organelles display subtly increased acidification in CF respiratory epithelial cells. Of further relev.....
Document: Azithromycin corrects organellar pH in CF lung epithelial cells. We tested the effects of AZT on CF respiratory epithelial cells in the absence of bacteria or microbial innate immunity agonists. Among the tests employed, we examine the pH of intracellular organelles since prior studies [27] [28] [29] [32] [33] [34] [35] have indicated that these organelles display subtly increased acidification in CF respiratory epithelial cells. Of further relevance, unlike most other macrolides that show little benefit in CF 14 , AZT possesses two weak base functional groups with pKa of 8.2 and 8.6 (Fig. 1A) . The pH of the lumen of the trans-Golgi network (TGN) and recycling endosomes (RE) in CF lung cells were measured by ratiometrically applying an intracellular pH-sensitive probe, pHlourin GFP 36 . The pH sensitive GFP was fused to TGN38 or cellubrevin thus localizing the pHluorin GFP to the lumen of the TGN or RE 36 in CF respiratory epithelial cells 35 34 . Primary CF bronchial epithelial cells treated with AZT displayed correction of the previously reported TGN and RE hyperacidifcation [27] [28] [29] [32] [33] [34] [35] (Fig. B-G) . Treatment of IB3-1 (CF cells) with either 100 µM (for 1 h) or 1 µM AZT (for 48 h), led to a correction of TGN pH from 6.2 ± 0.1 (control) to 7.1 ± 0.1 or to 6.7 ± 0.2 ( Fig. 1C) , comparable to the pH of 6.7 ± 0.1 within the TGN of S9 cells (CFTR-corrected IB3-1 cells). In primary CF bronchial epithelial cells (Fig 1D) , AZT treatment corrected their TGN pH from 6.1 ± 0.2 to 6.7 ± 0.1 (Fig 1D) . Of note is that the absolute concentration of AZT was not critical for the effect at equilibrium, as expected from the extracellular sink of an acidotropic agent accumulating in acidified compartments by being protonated and trapped within the organellar lumen.
Search related documents:
Co phrase search for related documents- Try single phrases listed below for: 1
Co phrase search for related documents, hyperlinks ordered by date