Human thrombin has been shown to stimulate monocyte chemstaxis, 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 (IFN gamma)-differentiated and nondifferentiated U937 monocytic cells. Northern blot analysis shows that PAR1 expression is upregulated upon differentiation. Experiments with biotinylated and I-125-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 mu g/ml (30-300 nM, concentrations where specific thrombin binding is observed) stimulates proliferation of IFN gamma-differentiated U937 cells but not of undifferentiated U937 cells. Thrombin also stimulates interleukin-6 (IL6) production in IFN gamma-differentiated U937 cells. Moreover, thrombin induces high levels of IL6, interleukin-1 beta (IL-1 beta), 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.

Naldini, A., Sower, L., Bocci, V., Meyers, B., Carney, D.H. (1998). Thrombin receptor expression and responsiveness of human monocytic cells to thrombin is linked to interferon-induced cellular differentiation. JOURNAL OF CELLULAR PHYSIOLOGY, 177(1), 76-84 [10.1002/(SICI)1097-4652(199810)177:1<76::AID-JCP8>3.0.CO;2-B].

Thrombin receptor expression and responsiveness of human monocytic cells to thrombin is linked to interferon-induced cellular differentiation

NALDINI, A.;BOCCI, V.;
1998-01-01

Abstract

Human thrombin has been shown to stimulate monocyte chemstaxis, 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 (IFN gamma)-differentiated and nondifferentiated U937 monocytic cells. Northern blot analysis shows that PAR1 expression is upregulated upon differentiation. Experiments with biotinylated and I-125-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 mu g/ml (30-300 nM, concentrations where specific thrombin binding is observed) stimulates proliferation of IFN gamma-differentiated U937 cells but not of undifferentiated U937 cells. Thrombin also stimulates interleukin-6 (IL6) production in IFN gamma-differentiated U937 cells. Moreover, thrombin induces high levels of IL6, interleukin-1 beta (IL-1 beta), 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.
1998
Naldini, A., Sower, L., Bocci, V., Meyers, B., Carney, D.H. (1998). Thrombin receptor expression and responsiveness of human monocytic cells to thrombin is linked to interferon-induced cellular differentiation. JOURNAL OF CELLULAR PHYSIOLOGY, 177(1), 76-84 [10.1002/(SICI)1097-4652(199810)177:1<76::AID-JCP8>3.0.CO;2-B].
File in questo prodotto:
File Dimensione Formato  
Thrombin receptor expression and responsiveness of human monocytic cells to thrombin is linked to interferon -induced cellular differentiation (JourCellP) 1998) .pdf

non disponibili

Tipologia: Abstract
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 7.36 MB
Formato Adobe PDF
7.36 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/8368
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo