PMID- 12805069
OWN - NLM
STAT- MEDLINE
DCOM- 20031029
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 102
IP  - 7
DP  - 2003 Oct 1
TI  - Differential expression and regulation of protease-activated receptors in human 
      peripheral monocytes and monocyte-derived antigen-presenting cells.
PG  - 2645-52
AB  - Protease-activated receptors (PARs) are stimulated by proteolytic cleavage of 
      their extracellular domain, unmasking a new N-terminus acting as tethered ligand. 
      Whereas the role of PARs in platelets is well known, their presence and function 
      in human monocytes and other antigen-presenting cells has not been characterized. 
      Here it is demonstrated that human peripheral monocytes and monocyte-derived 
      macrophages and dendritic cells differentially express PARs. Human monocytes 
      express mainly PAR1 and less PAR3. Differentiation of monocytes into macrophages 
      by either macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage 
      colony-stimulating factor (GM-CSF) elicits enhanced expression of PAR1, PAR2, and 
      PAR3. In contrast, dendritic cells differentiated from monocytes by GM-CSF and 
      interleukin-4 (IL-4) strongly down-regulated PAR1, PAR2, and PAR3, both at the 
      mRNA and the protein level. Down-regulation of the PAR expression was apparently 
      due to IL-4, because treatment of macrophages with IL-4 caused down-regulation of 
      PAR1, PAR2, and PAR3. PAR4 mRNA expression remained undetectable in any of the 
      cell types investigated. Stimulation of PAR1, PAR2, and PAR3 with thrombin, 
      trypsin, or established receptor-activating peptides (PAR-APs) triggered 
      cytosolic Ca2+ responses, indicating functionally active PARs. Further, 
      stimulation of monocytes or macrophages with thrombin or PAR1-AP, but not with 
      PAR2-or PAR4-AP, triggers expression of monocyte chemoattractant protein-1 
      (MCP-1) both at the mRNA and the protein level. These data demonstrate that 
      differentiation of human monocytes is associated with differential expression of 
      functionally active PARs that mediate distinct regulatory functions in 
      inflammation and atherogenesis.
FAU - Colognato, Renato
AU  - Colognato R
AD  - Department of Pharmacology of Natural Products and Clinical Pharmacology, 
      University of Ulm, Germany.
FAU - Slupsky, Joseph R
AU  - Slupsky JR
FAU - Jendrach, Marina
AU  - Jendrach M
FAU - Burysek, Ladislav
AU  - Burysek L
FAU - Syrovets, Tatiana
AU  - Syrovets T
FAU - Simmet, Thomas
AU  - Simmet T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030612
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hemostatics)
RN  - 0 (Receptor, PAR-1)
RN  - 0 (Receptor, PAR-2)
RN  - 0 (Receptors, Thrombin)
RN  - 0 (protease-activated receptor 3)
RN  - 207137-56-2 (Interleukin-4)
RN  - EC 3.4.21.5 (Thrombin)
RN  - JWE1M73YZN (protease-activated receptor 4)
SB  - IM
MH  - Antigen-Presenting Cells/cytology/*physiology
MH  - Calcium Signaling/immunology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics
MH  - Dendritic Cells/cytology/physiology
MH  - Down-Regulation/drug effects/immunology
MH  - Gene Expression/drug effects/immunology
MH  - Hemostatics/pharmacology
MH  - Humans
MH  - Interleukin-4/pharmacology
MH  - Macrophages/cytology/physiology
MH  - Monocytes/cytology/*physiology
MH  - Receptor, PAR-1
MH  - Receptor, PAR-2
MH  - Receptors, Thrombin/*genetics/*metabolism
MH  - Thrombin/pharmacology
EDAT- 2003/06/14 05:00
MHDA- 2003/10/30 05:00
CRDT- 2003/06/14 05:00
PHST- 2003/06/14 05:00 [pubmed]
PHST- 2003/10/30 05:00 [medline]
PHST- 2003/06/14 05:00 [entrez]
AID - S0006-4971(20)44100-X [pii]
AID - 10.1182/blood-2002-08-2497 [doi]
PST - ppublish
SO  - Blood. 2003 Oct 1;102(7):2645-52. doi: 10.1182/blood-2002-08-2497. Epub 2003 Jun 
      12.