PMID- 11301188
OWN - NLM
STAT- MEDLINE
DCOM- 20010503
LR  - 20191025
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 29
IP  - 4
DP  - 2001 Apr
TI  - Pro-apoptotic and anti-apoptotic effects of transferrin and transferrin-derived 
      glycans on hematopoietic cells and lymphocytes.
PG  - 477-89
AB  - The aim of this study was to test the hypothesis that transferrin (Tf) has 
      anti-apoptotic properties and thereby exerts a cytoprotective effect against 
      tissue damage induced by irradiation and other cytotoxic modalities. This 
      hypothesis was tested in several models, including in vitro human short-term 
      marrow cultures, subpopulations of marrow cells, particularly, CD56(+) natural 
      killer cells (and natural killer cell lines), and in vivo radioprotection of 
      murine marrow cells. Reverse transcriptase polymerase chain reaction analysis was 
      used for determination of cytokine mRNA. Preincubation of human marrow with Tf 
      protected cells (except for a CD56(+) subpopulation) against cell death induced 
      by gamma-irradiation, tumor necrosis factor-alpha (TNF-alpha), and agonistic 
      anti-Fas monoclonal antibody. Deglycosylation of Tf abrogated this action of Tf; 
      conversely, Tf-derived glycans (Tf-Gly) (but not glycans isolated from other 
      proteins) mimicked the effects of the intact Tf molecule on apoptosis. Antibodies 
      specific for the Tf receptor (CD71) did not block the effects of Tf or Tf-Gly on 
      apoptosis. Determination of cytokine mRNA in the course of Fas-mediated apoptosis 
      in the presence of Tf or Tf-Gly showed upregulation of mRNA for Fas ligand and 
      TNF-alpha in CD56(+) and downregulation of these transcripts along with 
      upregulation of mRNA for interleukin-10 in CD3(+) marrow cells. Under these 
      conditions, a distinct increase in Fas-associated phosphatase-1 message was 
      observed in CD3(+) cells that were protected by Tf or Tf-Gly against apoptosis. 
      The in vitro data were confirmed in a murine in vivo model in which pretreatment 
      of mice with Tf protected marrow cells against gamma-irradiation-induced cell 
      death. These data suggest a role for Tf and particularly Tf-Gly in the regulation 
      of programmed cell death, apparently via alterations in cytokine expression, and 
      provide a basis for additional studies on the use of Tf in cytoprotective 
      protocols.
FAU - Lesnikov, V
AU  - Lesnikov V
AD  - Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview 
      Avenue North, D1-100, PO Box 19024, Seattle, WA 98109-1024, USA. 
      vlesniko@fhcrc.org
FAU - Lesnikova, M
AU  - Lesnikova M
FAU - Deeg, H J
AU  - Deeg HJ
LA  - eng
GR  - HL36444/HL/NHLBI 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  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CD3 Complex)
RN  - 0 (CD56 Antigen)
RN  - 0 (Carrier Proteins)
RN  - 0 (Polysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transferrin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
RN  - EC 3.1.3.48 (PTPN13 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 13)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (Ptpn13 protein, mouse)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Apoptosis/*drug effects/radiation effects
MH  - Bone Marrow Cells/*cytology/drug effects
MH  - CD3 Complex/analysis
MH  - CD56 Antigen/analysis
MH  - Carrier Proteins/genetics
MH  - Cell Line
MH  - Female
MH  - Gamma Rays
MH  - Glycosylation
MH  - Humans
MH  - Interleukin-10/genetics
MH  - Killer Cells, Natural/*cytology/drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Polysaccharides/*pharmacology
MH  - Protein Phosphatase 1
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 13
MH  - Protein Tyrosine Phosphatases/genetics
MH  - RNA, Messenger/analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transferrin/*pharmacology
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - fas Receptor/immunology/physiology
EDAT- 2001/04/13 10:00
MHDA- 2001/05/05 10:01
CRDT- 2001/04/13 10:00
PHST- 2001/04/13 10:00 [pubmed]
PHST- 2001/05/05 10:01 [medline]
PHST- 2001/04/13 10:00 [entrez]
AID - S0301472X00006871 [pii]
AID - 10.1016/s0301-472x(00)00687-1 [doi]
PST - ppublish
SO  - Exp Hematol. 2001 Apr;29(4):477-89. doi: 10.1016/s0301-472x(00)00687-1.