PMID- 10233424
OWN - NLM
STAT- MEDLINE
DCOM- 19990624
LR  - 20131121
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 105
IP  - 2
DP  - 1999 May
TI  - The physiological response of thrombopoietin (c-Mpl ligand) to thrombocytopenia
      in the rat.
PG  - 478-85
AB  - It has been suggested that circulating levels of thrombopoietin (TPO) are
      determined primarily by platelet and megakaryocyte clearance of TPO and not by
      changes in hepatic TPO production. The experimental evidence accumulated so far
      to support this hypothesis is incomplete. We have therefore developed a new model
      of non-immune thrombocytopenia in the rat and used it to assess the relationship 
      of TPO (c-mpl ligand) to the platelet mass. 14 d following the administration of 
      busulphan, the platelet count reached a nadir of <2% of its initial value and
      remained at this level for up to 6 d. Circulating TPO was measured by two
      different bioassays which were sensitive enough to measure normal levels of TPO
      and levels rose from 106 +/- 29 pg/ml in animals with a normal platelet count to 
      2015 +/- 544 pg/ml in those with thrombocytopenia. These elevated levels of TPO
      were solely a response to the low platelet count since transfusion of a normal
      mass of platelets into the thrombocytopenic animals returned the TPO levels
      exactly to normal. The increase in TPO levels in thrombocytopenic animals was not
      due to increased TPO production since the thrombocytopenic animals did not show
      any increase in TPO mRNA in total or polysome-associated hepatic RNA. Rather, rat
      platelets were able to bind and stoichiometrically remove TPO from
      thrombocytopenic plasma via high-affinity receptors (Kd = 38 +/- 10 pm; 233 +/-
      32 receptors/platelet). These results serve as a proof that the circulating level
      of TPO is determined not by alterations in TPO transcription or translation but
      by the ability of the platelet mass to bind and remove TPO from the circulation.
FAU - Yang, C
AU  - Yang C
AD  - Hematology Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
FAU - Li, Y C
AU  - Li YC
FAU - Kuter, D J
AU  - Kuter DJ
LA  - eng
GR  - HL 54838/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (RNA, Messenger)
RN  - 9014-42-0 (Thrombopoietin)
RN  - G1LN9045DK (Busulfan)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/pharmacology
MH  - Blood Platelets/pathology
MH  - Busulfan/pharmacology
MH  - Male
MH  - Platelet Count
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Thrombocytopenia/*blood/pathology
MH  - Thrombopoietin/*metabolism
EDAT- 1999/05/08 00:00
MHDA- 1999/05/08 00:01
CRDT- 1999/05/08 00:00
PHST- 1999/05/08 00:00 [pubmed]
PHST- 1999/05/08 00:01 [medline]
PHST- 1999/05/08 00:00 [entrez]
PST - ppublish
SO  - Br J Haematol. 1999 May;105(2):478-85.