Exp Cell Res  2002 Nov 15;281(1):86-100 

Azithromycin, a lysosomotropic antibiotic, has distinct effects on fluid-phase
and receptor-mediated endocytosis, but does not impair phagocytosis in J774

Tyteca D, Van Der Smissen P, Mettlen M, Van Bambeke F, Tulkens PM,
Mingeot-Leclercq MP, Courtoy PJ.

Unite de Pharmacologie Cellulaire et Moleculaire, Universite Catholique de
Louvain, UCL 7370 Avenue E. Mounier 73, Brussels, Belgium.

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 gamma 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 inaccessible 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.

PMID: 12441132 [PubMed - indexed for MEDLINE]