Azithromycin, a Lysosomotropic Antibiotic, Has Distinct Effects on Fluid-Phase and Receptor-Mediated Endocytosis, but Does Not Impair Phagocytosis in J774 Macrophages

Authors: Tyteca D.¹; Van Der Smissen P.²; Mettlen M.²; Van Bambeke F.¹; Tulkens P.M.¹; Mingeot-Leclercq M-P.¹; Courtoy P.J.²

Source: Experimental Cell Research, Volume 281, Number 1, November 2002 , pp. 86-100(15)

Publisher: Academic Press

Abstract:

Pretreatment of J774 mouse macrophages by the dicationic macrolide antibiotic, azithromycin (AZ), selectively inhibited fluid-phase endocytosis of horseradish peroxidase and lucifer yellow, but not phagocytosis of latex beads. AZ delayed sequestration of receptor-bound transferrin and peroxidase–anti-peroxidase immune complexes into cell-surface endocytic pits and vesicles, but did not slow down the subsequent rate of receptor-mediated endocytosis. AZ down-regulated cell surface transferrin receptors, but not Fc receptors, by causing a major delay in the accessibility of internalized transferrin receptors to the recycling route, without slowing down subsequent efflux, resulting in redistribution of the surface pool to an intracellular pool. Acidotropic accumulation of AZ was associated with an extensive vacuolation of late endosomes/lysosomes, and these compartments became unaccessible to horseradish peroxidase and immune complexes, but not to latex beads. The inhibitory profile of AZ cannot be solely accounted for by vacuolation and interference with acidification. AZ may help in dissecting various steps of the endocytic apparatus such as lateral mobility of receptors at the plasma membrane, formation of clathrin-independent endocytic vesicles, orientation of transferrin receptors into the recycling route, and fusogenicity with lysosomes. © 2002 Elsevier Science (USA).

Keywords: endocytosis; HRP; lucifer yellow; transferrin; immune complexes; phagocytosis; macrolide; macrophages

Language: English

Document Type: Research article

DOI: http://dx.doi.org/10.1006/excr.2002.5613

Affiliations: 1: Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, UCL 7370 Avenue E. Mounier 73, Brussels, B-1200, Belgium 2: Unité de Biologie Cellulaire, Christian de Duve International Institute of Cellular and Molecular Pathology, UCL 7541 Avenue Hippocrate 75, Brussels, B-1200, Belgium

Publication date: 2002-11-01

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• By this author: Tyteca D. ;  Van Der Smissen P. ;  Mettlen M. ;  Van Bambeke F. ;  Tulkens P.M. ;  Mingeot-Leclercq M-P. ;  Courtoy P.J.

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