PMID- 12130531
OWN - NLM
STAT- MEDLINE
DCOM- 20020906
LR  - 20220330
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 100
IP  - 3
DP  - 2002 Aug 1
TI  - Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by 
      bone marrow-derived dendritic cells.
PG  - 1084-7
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.
FAU - Hackstein, Holger
AU  - Hackstein H
AD  - Thomas E. Starzl Transplantation Institute and Department of Surgery, University 
      of Pittsburgh, PA 15213, USA.
FAU - Taner, Timucin
AU  - Taner T
FAU - Logar, Alison J
AU  - Logar AJ
FAU - Thomson, Angus W
AU  - Thomson AW
LA  - eng
GR  - R01 AI41011/AI/NIAID NIH HHS/United States
GR  - R01 DK49745/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Mannose Receptor)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Receptors, Cell Surface)
RN  - W36ZG6FT64 (Sirolimus)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Cell Culture Techniques/methods
MH  - Dendritic Cells/cytology/*drug effects/physiology
MH  - Drug Antagonism
MH  - Endocytosis/*drug effects
MH  - Immunosuppressive Agents/administration & dosage/*pharmacology
MH  - *Lectins, C-Type
MH  - Male
MH  - Mannose Receptor
MH  - *Mannose-Binding Lectins
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pinocytosis/*drug effects
MH  - Receptors, Cell Surface/physiology
MH  - Sirolimus/administration & dosage/*pharmacology
MH  - Tacrolimus/pharmacology
EDAT- 2002/07/20 10:00
MHDA- 2002/09/07 10:01
CRDT- 2002/07/20 10:00
PHST- 2002/07/20 10:00 [pubmed]
PHST- 2002/09/07 10:01 [medline]
PHST- 2002/07/20 10:00 [entrez]
AID - S0006-4971(20)59419-6 [pii]
AID - 10.1182/blood.v100.3.1084 [doi]
PST - ppublish
SO  - Blood. 2002 Aug 1;100(3):1084-7. doi: 10.1182/blood.v100.3.1084.