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

Holger Hackstein, Timucin Taner, Alison J. Logar, Angus W. Thomson

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

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 II lo 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.

Original languageEnglish (US)
Pages (from-to)1084-1087
Number of pages4
JournalBlood
Volume100
Issue number3
DOIs
StatePublished - Aug 1 2002
Externally publishedYes

Fingerprint

Sirolimus
Endocytosis
Dendritic Cells
Bone
Bone Marrow
Flow cytometry
Immunosuppressive Agents
Albumin Receptors
Flow Cytometry
Macrolides
Tacrolimus
Antigen-Presenting Cells
Cell death
mannose receptor
Major Histocompatibility Complex
Fluorescein
Immunity
Cell Death
Color
Antigens

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells. / Hackstein, Holger; Taner, Timucin; Logar, Alison J.; Thomson, Angus W.

In: Blood, Vol. 100, No. 3, 01.08.2002, p. 1084-1087.

Research output: Contribution to journalArticle

Hackstein, Holger ; Taner, Timucin ; Logar, Alison J. ; Thomson, Angus W. / Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells. In: Blood. 2002 ; Vol. 100, No. 3. pp. 1084-1087.
@article{186baf941eba4d0cbf2c37ae996aeb65,
title = "Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells",
abstract = "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 II lo 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.",
author = "Holger Hackstein and Timucin Taner and Logar, {Alison J.} and Thomson, {Angus W.}",
year = "2002",
month = "8",
day = "1",
doi = "10.1182/blood.V100.3.1084",
language = "English (US)",
volume = "100",
pages = "1084--1087",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

TY - JOUR

T1 - Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells

AU - Hackstein, Holger

AU - Taner, Timucin

AU - Logar, Alison J.

AU - Thomson, Angus W.

PY - 2002/8/1

Y1 - 2002/8/1

N2 - 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 II lo 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.

AB - 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 II lo 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.

UR - http://www.scopus.com/inward/record.url?scp=0036682957&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036682957&partnerID=8YFLogxK

U2 - 10.1182/blood.V100.3.1084

DO - 10.1182/blood.V100.3.1084

M3 - Article

C2 - 12130531

AN - SCOPUS:0036682957

VL - 100

SP - 1084

EP - 1087

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -