TY - JOUR
T1 - Azithromycin, a lysosomotropic antibiotic, has distinct effects on fluid-phase and receptor-mediated endocytosis, but does not impair phagocytosis in J774 macrophages
AU - Tyteca, Donatienne
AU - Van Der Smissen, Patrick
AU - Mettlen, Marcel
AU - Van Bambeke, Françoise
AU - Tulkens, Paul M.
AU - Mingeot-Leclercq, Marie Paule
AU - Courtoy, Pierre J.
N1 - Funding Information:
The skillful technical assistance of N. Aguilera, F. Andries-Ren-oird, M.-C. Cambier, T. Lac, M. Leruth, and F. Pyrrhon-N’Kuli as well as the excellent secretarial assistance of Y. Marchand is gratefully acknowledged. Ph. de Diesbach collaborated in some experiments. D.T. was a Research Fellow, F.V.B. a Research Associate, and M.P.M. a Senior Research Associate of the Belgian Fonds National de la Recherche Scientifique (FNRS). This work was supported by grants from the Belgian FNRS (1.5206.99 to P.T.) and the Belgian Fonds de la Recherche Scientifique Médicale (FRSM 3.4.549.00 to P.T., 3.4.546.02 to M.P.M. and 3.4621.01 to P.C.), the Actions de Recherches Concertées of the Direction Générale de la Recherche Scientifique–Communauté Franc¸aise de Belgique (Contract 94/99-172 to P.T., M.P.M., and P.C. and 99/04-236 to P.C.), and the Interuniversity Attraction Poles (to P.C.).
PY - 2002
Y1 - 2002
N2 - 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 Fcγ 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.
AB - 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 Fcγ 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.
KW - Endocytosis
KW - HRP
KW - Immune complexes
KW - Lucifer yellow
KW - Macrolide
KW - Macrophages
KW - Phagocytosis
KW - Transferrin
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U2 - 10.1006/excr.2002.5613
DO - 10.1006/excr.2002.5613
M3 - Article
C2 - 12441132
AN - SCOPUS:0036438489
SN - 0014-4827
VL - 281
SP - 86
EP - 100
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -