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Blood, 1 August 2002, Vol. 100, No. 3, pp. 1084-1087
BRIEF REPORT
Rapamycin inhibits macropinocytosis and mannose
receptor-mediated endocytosis by bone marrow-derived dendritic
cells
Holger Hackstein,
Timucin Taner,
Alison J. Logar, and
Angus W. Thomson
From the Thomas E. Starzl Transplantation Institute and
Department of Surgery and the Department of Molecular Genetics and
Biochemistry, University of Pittsburgh, PA, and the Institute of
Clinical Immunology and Transfusion Medicine, Justus-Liebig University,
Giessen, Germany.
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.

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