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

Donatienne Tyteca, Patrick Van Der Smissen, Marcel Mettlen, Françoise Van Bambeke, Paul M. Tulkens, Marie Paule Mingeot-Leclercq, Pierre J. Courtoy

Research output: Contribution to journalArticle

52 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)86-100
Number of pages15
JournalExperimental Cell Research
Volume281
Issue number1
DOIs
StatePublished - Jan 1 2002

Keywords

  • Endocytosis
  • HRP
  • Immune complexes
  • Lucifer yellow
  • Macrolide
  • Macrophages
  • Phagocytosis
  • Transferrin

ASJC Scopus subject areas

  • Cell Biology

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