Rapamycin inhibits macropinocytosis and mannose receptor–mediated endocytosis by bone marrow–derived dendritic cells

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that use 2 major pathways for antigen uptake: constitutive macropinocytosis and mannose receptor–mediated endocytosis. Efficient endocytosis is critical for DCs to fulfill their sentinel function in immunity. We investigated the...

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Bibliographic Details
Published in:Blood 2002-08, Vol.100 (3), p.1084-1087
Main Authors: Hackstein, Holger, Taner, Timucin, Logar, Alison J., Thomson, Angus W.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Bone Marrow Cells - cytology
Cell Culture Techniques - methods
Dendritic Cells - cytology
Dendritic Cells - drug effects
Dendritic Cells - physiology
Drug Antagonism
Endocytosis - drug effects
Immunomodulators
Immunosuppressive Agents - administration & dosage
Immunosuppressive Agents - pharmacology
Lectins, C-Type
Male
Mannose-Binding Lectins
Medical sciences
Mice
Mice, Inbred C57BL
Pharmacology. Drug treatments
Pinocytosis - drug effects
Receptors, Cell Surface - physiology
Sirolimus - administration & dosage
Sirolimus - pharmacology
Tacrolimus - pharmacology
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Summary:Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that use 2 major pathways for antigen uptake: constitutive macropinocytosis and mannose receptor–mediated endocytosis. Efficient endocytosis is critical for DCs to fulfill their sentinel function in immunity. We investigated the influence of the immunosuppressive macrolide rapamycin on macropinocytosis of fluorescein isothiocyanate (FITC)–albumin and mannose receptor–mediated endocytosis of FITC-dextran by murine bone marrow–derived DCs by flow cytometry. The data show that (1) at a low, physiologically relevant concentration (1 ng/mL), rapamycin impairs macropinocytosis and mannose receptor–mediated endocytosis; (2) the effects are independent of DC maturation and can be demonstrated specifically in immature CD11c+ major histocompatibility complex (MHC) class IIlo DCs by 3-color flow cytometry; (3) inhibition of endocytosis is not related to apoptotic cell death; and (4) molar excess of the structurally related molecule FK506 inhibits the actions of rapamycin. The inhibitory effects of rapamycin on DC endocytosis were confirmed in vivo. To our knowledge, this is the first report that a clinically relevant immunosuppressant inhibits DC endocytosis.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V100.3.1084