PMID- 9731747
OWN - NLM
STAT- MEDLINE
DCOM- 19980921
LR  - 20081121
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 177
IP  - 1
DP  - 1998 Oct
TI  - Thrombin receptor expression and responsiveness of human monocytic cells to 
      thrombin is linked to interferon-induced cellular differentiation.
PG  - 76-84
AB  - Human thrombin has been shown to stimulate monocyte chemotaxis, phagocytosis, and 
      interleukin (IL8) production, but the mechanisms responsible for stimulation are 
      not well defined. In some cells, thrombin stimulation of proliferation appears to 
      require both cleavage of the proteolytically activated receptor for thrombin 
      (PAR1) and activation of a nonproteolytically activated thrombin receptor 
      (N-PAR), while in others activation of either receptor alone may be sufficient 
      for stimulation. We, therefore, have initiated studies to address thrombin 
      receptor expression and cell responsiveness to thrombin in interferon gamma 
      (IFNgamma)-differentiated and nondifferentiated U937 monocytic cells. Northern 
      blot analysis shows that PAR1 expression is upregulated upon differentiation. 
      Experiments with biotinylated and 125I-thrombin show that specific thrombin 
      binding is dramatically increased by differentiation although it is not clear if 
      this binding is to PAR1 or to a separate binding component such as N-PAR which is 
      present on fibroblasts and other cells. Addition of thrombin at concentrations of 
      1-10 microg/ml (30-300 nM, concentrations where specific thrombin binding is 
      observed) stimulates proliferation of IFNgamma-differentiated U937 cells but not 
      of undifferentiated U937 cells. Thrombin also stimulates interleukin-6 (IL6) 
      production in IFNgamma-differentiated U937 cells. Moreover, thrombin induces high 
      levels of IL6, interleukin-1beta (IL1beta), and tumor necrosis factor-alpha (TNF 
      alpha) production by peripheral blood mononuclear cells (PBMC) and monocytes. 
      These results show that differentiated U937 cells and mature PBMC are responsive 
      to thrombin whereas nondifferentiated U937 are not. Further, this responsiveness 
      appears to correlate with expression of PAR1 and to a dramatic increase in 
      specific thrombin binding. That thrombin stimulates cytokine production and 
      proliferation in populations of differentiated monocytes suggests that thrombin 
      may be an important regulator of inflammation and wound healing.
FAU - Naldini, A
AU  - Naldini A
AD  - University of Siena, Institute of General Physiology, Italy. Naldini@unisi.it
FAU - Sower, L
AU  - Sower L
FAU - Bocci, V
AU  - Bocci V
FAU - Meyers, B
AU  - Meyers B
FAU - Carney, D H
AU  - Carney DH
LA  - eng
GR  - GM-47572/GM/NIGMS 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  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Thrombin)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Cell Differentiation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Interferon-gamma/*pharmacology
MH  - Interleukin-6/biosynthesis/metabolism
MH  - Kinetics
MH  - Leukemia, Promyelocytic, Acute
MH  - Monocytes/chemistry/*cytology/drug effects
MH  - Receptors, Thrombin/*genetics
MH  - Thrombin/*pharmacology
MH  - Tumor Cells, Cultured/chemistry/drug effects/metabolism
EDAT- 1998/09/10 02:03
MHDA- 2000/06/20 09:00
CRDT- 1998/09/10 02:03
PHST- 1998/09/10 02:03 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1998/09/10 02:03 [entrez]
AID - 10.1002/(SICI)1097-4652(199810)177:1<76::AID-JCP8>3.0.CO;2-B [pii]
AID - 10.1002/(SICI)1097-4652(199810)177:1<76::AID-JCP8>3.0.CO;2-B [doi]
PST - ppublish
SO  - J Cell Physiol. 1998 Oct;177(1):76-84. doi: 
      10.1002/(SICI)1097-4652(199810)177:1<76::AID-JCP8>3.0.CO;2-B.