SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on June 12, 2003; DOI 10.1182/blood-2002-08-2497. This Article Full Text (PDF) All Versions of this Article: 2002-08-2497v1 102/7/2645    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Colognato, R. Articles by Simmet, T. Search for Related Content PubMed PubMed Citation Articles by Colognato, R. Articles by Simmet, T. Social Bookmarking                   What's this? Submitted August 14, 2002 Accepted April 7, 2003 Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells Renato Colognato, Joseph R Slupsky, Marina Jendrach, Ladislav Burysek, Tatiana Syrovets, and Thomas Simmet* Department of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Ulm, Germany * Corresponding author; email: thomas.simmet{at}medizin.uni-ulm.de. 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 (IL)-4 strongly downregulated PAR1, PAR2, and PAR3, both at the mRNA and the protein level. Downregulation of the PAR expression was apparently due to IL-4, because treatment of macrophages with IL-4 caused downregulation 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-AP) 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 (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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. I. Borissoff, H. M.H. Spronk, S. Heeneman, and H. ten Cate Is thrombin a key player in the 'coagulation-atherogenesis' maze? Cardiovasc Res, June 1, 2009; 82(3): 392 - 403. [Abstract] [Full Text] [PDF] P. F. Mercer, R. H. Johns, C. J. Scotton, M. A. Krupiczojc, M. Konigshoff, D. C. J. Howell, R. J. McAnulty, A. Das, A. J. Thorley, T. D. Tetley, et al. Pulmonary Epithelium Is a Prominent Source of Proteinase-activated Receptor-1-inducible CCL2 in Pulmonary Fibrosis Am. J. Respir. Crit. Care Med., March 1, 2009; 179(5): 414 - 425. [Abstract] [Full Text] [PDF] E Hyun, P Andrade-Gordon, M Steinhoff, and N Vergnolle Protease-activated receptor-2 activation: a major actor in intestinal inflammation Gut, September 1, 2008; 57(9): 1222 - 1229. [Abstract] [Full Text] [PDF] L. J. Toltl, S. Beaudin, P. C. Liaw, and and the Canadian Critical Care Translational Biolo Activated Protein C Up-Regulates IL-10 and Inhibits Tissue Factor in Blood Monocytes J. Immunol., August 1, 2008; 181(3): 2165 - 2173. [Abstract] [Full Text] [PDF] X. Li, T. Syrovets, S. Paskas, Y. Laumonnier, and T. Simmet Mature Dendritic Cells Express Functional Thrombin Receptors Triggering Chemotaxis and CCL18/Pulmonary and Activation-Regulated Chemokine Induction J. Immunol., July 15, 2008; 181(2): 1215 - 1223. [Abstract] [Full Text] [PDF] V. Shpacovitch, M. Feld, M. D. Hollenberg, T. A. Luger, and M. Steinhoff Role of protease-activated receptors in inflammatory responses, innate and adaptive immunity J. Leukoc. Biol., June 1, 2008; 83(6): 1309 - 1322. [Abstract] [Full Text] [PDF] M. Feld, V. M. Shpacovitch, C. Ehrhardt, C. Kerkhoff, M. D. Hollenberg, N. Vergnolle, S. Ludwig, and M. Steinhoff Agonists of Proteinase-Activated Receptor-2 Enhance IFN-{gamma}-Inducible Effects on Human Monocytes: Role in Influenza A Infection J. Immunol., May 15, 2008; 180(10): 6903 - 6910. [Abstract] [Full Text] [PDF] C. Cuaz-Perolin, L. Billiet, E. Bauge, C. Copin, D. Scott-Algara, F. Genze, B. Buchele, T. Syrovets, T. Simmet, and M. Rouis Antiinflammatory and Antiatherogenic Effects of the NF-{kappa}B Inhibitor Acetyl-11-Keto-{beta}-Boswellic Acid in LPS-Challenged ApoE-/- Mice Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 272 - 277. [Abstract] [Full Text] [PDF] T. J. Moraes, R. Martin, J. D. Plumb, E. Vachon, C. M. Cameron, A. Danesh, D. J. Kelvin, W. Ruf, and G. P. Downey Role of PAR2 in murine pulmonary pseudomonal infection Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L368 - L377. [Abstract] [Full Text] [PDF] J. Lattin, D. A. Zidar, K. Schroder, S. Kellie, D. A. Hume, and M. J. Sweet G-protein-coupled receptor expression, function, and signaling in macrophages J. Leukoc. Biol., July 1, 2007; 82(1): 16 - 32. [Abstract] [Full Text] [PDF] J. Ahamed, F. Niessen, T. Kurokawa, Y. K. Lee, G. Bhattacharjee, J. H. Morrissey, and W. Ruf Regulation of macrophage procoagulant responses by the tissue factor cytoplasmic domain in endotoxemia Blood, June 15, 2007; 109(12): 5251 - 5259. [Abstract] [Full Text] [PDF] Q. Li, Y. Laumonnier, T. Syrovets, and T. Simmet Plasmin Triggers Cytokine Induction in Human Monocyte-Derived Macrophages Arterioscler Thromb Vasc Biol, June 1, 2007; 27(6): 1383 - 1389. [Abstract] [Full Text] [PDF] N. Lippuner, B. Morell, A. Schaffner, and D. J. Schaer Proteinase-activated receptors induce nonoxidative, antimicrobial peptides and increased antimicrobial activity in human mononuclear phagocytes J. Leukoc. Biol., February 1, 2007; 81(2): 465 - 473. [Abstract] [Full Text] [PDF] D. A. Stephenson, L. J. Toltl, S. Beaudin, and P. C. Liaw Modulation of Monocyte Function by Activated Protein C, a Natural Anticoagulant J. Immunol., August 15, 2006; 177(4): 2115 - 2122. [Abstract] [Full Text] [PDF] E. Csernok, M. Ai, W. L. Gross, D. Wicklein, A. Petersen, B. Lindner, P. Lamprecht, J. U. Holle, and B. Hellmich Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway Blood, June 1, 2006; 107(11): 4440 - 4448. [Abstract] [Full Text] [PDF] Y. Laumonnier, T. Syrovets, L. Burysek, and T. Simmet Identification of the annexin A2 heterotetramer as a receptor for the plasmin-induced signaling in human peripheral monocytes Blood, April 15, 2006; 107(8): 3342 - 3349. [Abstract] [Full Text] [PDF] F. Noorbakhsh, S. Tsutsui, N. Vergnolle, L. A. Boven, N. Shariat, M. Vodjgani, K. G. Warren, P. Andrade-Gordon, M. D. Hollenberg, and C. Power Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis J. Exp. Med., February 21, 2006; 203(2): 425 - 435. [Abstract] [Full Text] [PDF] K. E. Welty-Wolf, M. S. Carraway, T. L. Ortel, A. J. Ghio, S. Idell, J. Egan, X. Zhu, J.-a. Jiao, H. C. Wong, and C. A. Piantadosi Blockade of tissue factor-factor X binding attenuates sepsis-induced respiratory and renal failure Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L21 - L31. [Abstract] [Full Text] [PDF] U. Johansson, C. Lawson, M. Dabare, D. Syndercombe-Court, A. C. Newland, G. L. Howells, and M. G. Macey Human peripheral blood monocytes express protease receptor-2 and respond to receptor activation by production of IL-6, IL-8, and IL-1{beta} J. Leukoc. Biol., October 1, 2005; 78(4): 967 - 975. [Abstract] [Full Text] [PDF] A. Naldini, C. Bernini, A. Pucci, and F. Carraro Thrombin-mediated IL-10 up-regulation involves protease-activated receptor (PAR)-1 expression in human mononuclear leukocytes J. Leukoc. Biol., September 1, 2005; 78(3): 736 - 744. [Abstract] [Full Text] [PDF] A. Schaffner, P. Rhyn, G. Schoedon, and D. J. Schaer Regulated expression of platelet factor 4 in human monocytes--role of PARs as a quantitatively important monocyte activation pathway J. Leukoc. Biol., July 1, 2005; 78(1): 202 - 209. [Abstract] [Full Text] [PDF] J. Ahamed, M. Belting, and W. Ruf Regulation of tissue factor-induced signaling by endogenous and recombinant tissue factor pathway inhibitor 1 Blood, March 15, 2005; 105(6): 2384 - 2391. [Abstract] [Full Text] [PDF] T. Syrovets, J. E. Gschwend, B. Buchele, Y. Laumonnier, W. Zugmaier, F. Genze, and T. Simmet Inhibition of I{kappa}B Kinase Activity by Acetyl-boswellic Acids Promotes Apoptosis in Androgen-independent PC-3 Prostate Cancer Cells in Vitro and in Vivo J. Biol. Chem., February 18, 2005; 280(7): 6170 - 6180. [Abstract] [Full Text] [PDF] M. Steinhoff, J. Buddenkotte, V. Shpacovitch, A. Rattenholl, C. Moormann, N. Vergnolle, T. A. Luger, and M. D. Hollenberg Proteinase-Activated Receptors: Transducers of Proteinase-Mediated Signaling in Inflammation and Immune Response Endocr. Rev., February 1, 2005; 26(1): 1 - 43. [Abstract] [Full Text] [PDF] T. Syrovets, B. Buchele, C. Krauss, Y. Laumonnier, and T. Simmet Acetyl-Boswellic Acids Inhibit Lipopolysaccharide-Mediated TNF-{alpha} Induction in Monocytes by Direct Interaction with I{kappa}B Kinases J. Immunol., January 1, 2005; 174(1): 498 - 506. [Abstract] [Full Text] [PDF] J. Ahamed and W. Ruf Protease-activated Receptor 2-dependent Phosphorylation of the Tissue Factor Cytoplasmic Domain J. Biol. Chem., May 28, 2004; 279(22): 23038 - 23044. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020