PMID- 9028319
OWN - NLM
STAT- MEDLINE
DCOM- 19970311
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 89
IP  - 3
DP  - 1997 Feb 1
TI  - Thrombopoietin enhances the alpha IIb beta 3-dependent adhesion of megakaryocytic 
      cells to fibrinogen or fibronectin through PI 3 kinase.
PG  - 883-95
AB  - The effect of thrombopoietin (TPO) on the functional activity of surface alpha 
      IIb beta 3 (GPIIbIIIa) was investigated in both primary human megakaryocytic 
      cells, derived from peripheral blood CD34+ cells, and HEL hematopoietic cell 
      line. TPO (100 ng/mL) induced a sixfold to ninefold enhancement of adhesion of 
      both primary megakaryocytic and HEL cells to plates coated with either fibrinogen 
      or fibronectin and a parallel increase of immunoreactivity to the PAC1 monoclonal 
      antibody (MoAb) and fluorescein isothiocyanate-fibrinogen, both of which 
      recognize an activated state of alpha IIb beta 3. The enhanced adhesion to 
      fibrinogen or fibronectin was mediated by the Arg-Gly-Asp (RGD) recognition 
      sequence of alpha IIb beta 3, as it was abolished by pretreatment of cells with 
      saturating concentrations of RGDS peptide. A MoAb specific for the alpha IIb beta 
      subunit of alpha IIb beta 3 also inhibited cell attachment to fibrinogen or 
      fibronectin, while MoAb to anti-alpha v beta 3 or anti-alpha 5 integrins were 
      completely ineffective, clearly indicating that alpha IIb beta 3 participates in 
      this association. A role for PI 3 kinase (PI 3-K) in the TPO-mediated increase in 
      alpha IIb beta 3 function in megakaryocytic cells was suggested by the ability of 
      the PI 3-K inhibitor wortmannin (100 nmol/L) and antisense oligonucleotides 
      directed against the p85 regulatory subunit of PI 3-K to completely block the 
      TPO-induced increase in alpha IIb beta 3 integrin activity upon TPO stimulation. 
      The modulation of adhesiveness to extracellular matrix proteins containing the 
      RGD motif mediated by TPO likely plays a physiologic role in 
      megakaryocytopoiesis, as pretreatment of CD34+ cells with RGDS or anti-alpha IIb 
      MoAb significantly reduced the number of megakaryocytic colonies obtained in a 
      fibrinclot semisolid assay.
FAU - Zauli, G
AU  - Zauli G
AD  - Institute of Human Anatomy, University of Ferrara, Italy.
FAU - Bassini, A
AU  - Bassini A
FAU - Vitale, M
AU  - Vitale M
FAU - Gibellini, D
AU  - Gibellini D
FAU - Celeghini, C
AU  - Celeghini C
FAU - Caramelli, E
AU  - Caramelli E
FAU - Pierpaoli, S
AU  - Pierpaoli S
FAU - Guidotti, L
AU  - Guidotti L
FAU - Capitani, S
AU  - Capitani S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Actins)
RN  - 0 (Androstadienes)
RN  - 0 (Antigens, CD34)
RN  - 0 (Fibronectins)
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 9001-31-4 (Fibrin)
RN  - 9001-32-5 (Fibrinogen)
RN  - 9014-42-0 (Thrombopoietin)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Actins/biosynthesis
MH  - Androstadienes/pharmacology
MH  - Antigens, CD34/pharmacology
MH  - Blood Coagulation
MH  - Blood Platelets/drug effects/physiology
MH  - Cell Adhesion/drug effects
MH  - Cell Division/drug effects
MH  - Enzyme Activation/drug effects
MH  - Fibrin
MH  - Fibrinogen/drug effects/*metabolism
MH  - Fibronectins/drug effects/*metabolism
MH  - Humans
MH  - Leukemia, Erythroblastic, Acute
MH  - Megakaryocytes/*drug effects/enzymology/*physiology
MH  - Phosphatidylinositol 3-Kinases
MH  - Phosphotransferases (Alcohol Group Acceptor)/antagonists & 
      inhibitors/metabolism/*physiology
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/biosynthesis/drug effects/*physiology
MH  - Protein Binding/drug effects
MH  - Thrombopoietin/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
MH  - Wortmannin
EDAT- 1997/02/01 00:00
MHDA- 1997/02/01 00:01
CRDT- 1997/02/01 00:00
PHST- 1997/02/01 00:00 [pubmed]
PHST- 1997/02/01 00:01 [medline]
PHST- 1997/02/01 00:00 [entrez]
AID - S0006-4971(20)58891-5 [pii]
PST - ppublish
SO  - Blood. 1997 Feb 1;89(3):883-95.