This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Colotta, F. Articles by Mantovani, A. Search for Related Content PubMed PubMed Citation Articles by Colotta, F. Articles by Mantovani, A.

American Journal of Pathology, Vol 144, 975-985, Copyright © 1994 by American Society for Investigative Pathology

REGULAR ARTICLES

Expression of monocyte chemotactic protein-1 by monocytes and endothelial cells exposed to thrombin

F Colotta, FL Sciacca, M Sironi, W Luini, MJ Rabiet and A Mantovani
Centro Daniela e Catullo Borgomainerio, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

Thrombin, in addition to being a key enzyme in hemostasis, affects a series of endothelial and leukocyte functions and thus may be involved in the regulation of inflammatory reactions. Because leukocyte recruitment and activation are important events in inflammatory and thrombotic processes, in this study we have examined the possibility that thrombin induces the production of a cytokine chemotactic for mononuclear phagocytes. Human peripheral blood mononuclear cells (PBMC) exposed in vitro to thrombin expressed transcripts of monocyte chemotactic protein-1 (MCP-1; alternative acronyms: JE, monocyte chemotactic and activating factor, tumor-derived chemotactic factor). Thrombin was two- to threefold less effective than endotoxin in inducing MCP-1 transcripts in PBMC. Among circulating mononuclear cells, monocytes were identified as the cells expressing MCP-1 in response to thrombin. Monocytes expressed thrombin receptor transcripts. Boiling, hirudin, antithrombin III, and mutation of the catalytic site serine 205 into alanine) blocked the capacity of thrombin to induce MCP-1 expression. The thrombin receptor-activating peptide mimicked the effect of thrombin in inducing MCP-1 expression. Induction of MCP-1 transcript by thrombin was not reduced by blocking interleukin-1 and tumor necrosis factor, suggesting that these mediators are not involved in thrombin-induced expression of MCP-1. In addition to monocytes, endothelial cells (EC) also expressed MCP-1 in response to thrombin, although at lower levels compared with monocytes. Actinomycin D experiments indicated that induction of MCP-1 by thrombin in PBMC and EC was gene transcription dependent. The inhibition of protein synthesis blocked thrombin-induced MCP-1 expression in PBMC, whereas it superinduced both constitutive and thrombin-inducible expression of MCP-1 in EC, indicating different mechanisms of regulation of this gene in mononuclear phagocytes versus endothelial cells. Thrombin stimulated mononuclear cells and EC to release chemotactic activity for monocytes that could be inhibited by absorption with anti-MCP-1 antibodies. Induction of a chemotactic cytokine for monocytes by thrombin points to the importance of this enzyme in regulating inflammatory processes and further indicates that hemostasis, inflammation, and immunity are strictly interconnected processes.

This article has been cited by other articles:

				X. Deng, P. F. Mercer, C. J. Scotton, A. Gilchrist, and R. C. Chambers Thrombin Induces Fibroblast CCL2/JE Production and Release via Coupling of PAR1 to G{alpha}q and Cooperation between ERK1/2 and Rho Kinase Signaling Pathways Mol. Biol. Cell, June 1, 2008; 19(6): 2520 - 2533. [Abstract] [Full Text] [PDF]

				E. Camerer, I. Cornelissen, H. Kataoka, D. N. Duong, Y.-W. Zheng, and S. R. Coughlin Roles of protease-activated receptors in a mouse model of endotoxemia Blood, May 15, 2006; 107(10): 3912 - 3921. [Abstract] [Full Text] [PDF]

				Z. Lin, A. Hamik, R. Jain, A. Kumar, and M. K. Jain Kruppel-Like Factor 2 Inhibits Protease Activated Receptor-1 Expression and Thrombin-Mediated Endothelial Activation Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1185 - 1185. [Abstract] [Full Text] [PDF]

				A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]

				E. A. Lidington, R. Steinberg, A. R. Kinderlerer, R. C. Landis, M. Ohba, A. Samarel, D. O. Haskard, and J. C. Mason A role for proteinase-activated receptor 2 and PKC-{epsilon} in thrombin-mediated induction of decay-accelerating factor on human endothelial cells Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1437 - C1447. [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]

				G. Pertosa, S. Simone, M. Soccio, D. Marrone, L. Gesualdo, F. P. Schena, and G. Grandaliano Coagulation Cascade Activation Causes CC Chemokine Receptor-2 Gene Expression and Mononuclear Cell Activation in Hemodialysis Patients J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2477 - 2486. [Abstract] [Full Text] [PDF]

				D. C.J. Howell, R. H. Johns, J. A. Lasky, B. Shan, C. J. Scotton, G. J. Laurent, and R. C. Chambers Absence of Proteinase-Activated Receptor-1 Signaling Affords Protection from Bleomycin-Induced Lung Inflammation and Fibrosis Am. J. Pathol., May 1, 2005; 166(5): 1353 - 1365. [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. Shimizu, J. Nishihira, H. Watanabe, R. Abe, A. Honda, T. Ishibashi, and H. Shimizu Macrophage Migration Inhibitory Factor Is Induced by Thrombin and Factor Xa in Endothelial Cells J. Biol. Chem., April 2, 2004; 279(14): 13729 - 13737. [Abstract] [Full Text] [PDF]

				T. Minami, A. Sugiyama, S.-Q. Wu, R. Abid, T. Kodama, and W. C. Aird Thrombin and Phenotypic Modulation of the Endothelium Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 41 - 53. [Abstract] [Full Text] [PDF]

				H. Kataoka, J. R. Hamilton, D. D. McKemy, E. Camerer, Y.-W. Zheng, A. Cheng, C. Griffin, and S. R. Coughlin Protease-activated receptors 1 and 4 mediate thrombin signaling in endothelial cells Blood, November 1, 2003; 102(9): 3224 - 3231. [Abstract] [Full Text] [PDF]

				Y. Hirota, Y. Osuga, O. Yoshino, K. Koga, T. Yano, T. Hirata, E. Nose, T. Ayabe, A. Namba, O. Tsutsumi, et al. Possible Roles of Thrombin-Induced Activation of Protease-Activated Receptor 1 in Human Luteinized Granulosa Cells J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3952 - 3957. [Abstract] [Full Text] [PDF]

				S. B. Yee, J. R. Harkema, P. E. Ganey, and R. A. Roth The Coagulation System Contributes to Synergistic Liver Injury from Exposure to Monocrotaline and Bacterial Lipopolysaccharide Toxicol. Sci., August 1, 2003; 74(2): 457 - 469. [Abstract] [Full Text] [PDF]

				C. D. Major, R. J. Santulli, C. K. Derian, and P. Andrade-Gordon Extracellular Mediators in Atherosclerosis and Thrombosis: Lessons From Thrombin Receptor Knockout Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2003; 23(6): 931 - 939. [Abstract] [Full Text] [PDF]

				E. Belnoue, M. Kayibanda, J.-C. Deschemin, M. Viguier, M. Mack, W. A. Kuziel, and L. Renia CCR5 deficiency decreases susceptibility to experimental cerebral malaria Blood, June 1, 2003; 101(11): 4253 - 4259. [Abstract] [Full Text] [PDF]

				W. C. Aird The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome Blood, May 15, 2003; 101(10): 3765 - 3777. [Abstract] [Full Text] [PDF]

				E. de Jonge, P. W. Friederich, G. P. Vlasuk, W. E. Rote, M. B. Vroom, M. Levi, and T. van der Poll Activation of Coagulation by Administration of Recombinant Factor VIIa Elicits Interleukin 6 (IL-6) and IL-8 Release in Healthy Human Subjects Clin. Vaccine Immunol., May 1, 2003; 10(3): 495 - 497. [Abstract] [Full Text] [PDF]

				E. N. Morgan, T. H. Pohlman, C. Vocelka, A. Farr, G. Lindley, W. Chandler, J. M. Griscavage-Ennis, and E. D. Verrier Nuclear factor {kappa}B mediates a procoagulant response in monocytes during extracorporeal circulation J. Thorac. Cardiovasc. Surg., January 1, 2003; 125(1): 165 - 171. [Abstract] [Full Text] [PDF]

				S.-Q. Wu, T. Minami, D. J. Donovan, and W. C. Aird The proximal serum response element in the Egr-1 promoter mediates response to thrombin in primary human endothelial cells Blood, December 15, 2002; 100(13): 4454 - 4461. [Abstract] [Full Text] [PDF]

				T. Minami and W. C. Aird Thrombin Stimulation of the Vascular Cell Adhesion Molecule-1 Promoter in Endothelial Cells Is Mediated by Tandem Nuclear Factor-kappa B and GATA Motifs J. Biol. Chem., December 7, 2001; 276(50): 47632 - 47641. [Abstract] [Full Text] [PDF]

				R. D. Ye Regulation of nuclear factor {kappa}B activation by G-protein-coupled receptors J. Leukoc. Biol., December 1, 2001; 70(6): 839 - 848. [Abstract] [Full Text] [PDF]

				D. C. Morris, L. Zhang, Z. G. Zhang, M. Lu, K. L. Berens, P. M. Brown, and M. Chopp Extension of the Therapeutic Window for Recombinant Tissue Plasminogen Activator With Argatroban in a Rat Model of Embolic Stroke Stroke, November 1, 2001; 32(11): 2635 - 2640. [Abstract] [Full Text] [PDF]

				G. C. Auld, H. Ritchie, L. A. Robbie, and N. A. Booth Thrombin Upregulates Tissue Transglutaminase in Endothelial Cells: A Potential Role for Tissue Transglutaminase in Stability of Atherosclerotic Plaque Arterioscler. Thromb. Vasc. Biol., October 1, 2001; 21(10): 1689 - 1694. [Abstract] [Full Text] [PDF]

				V. Marin, F. A. Montero-Julian, S. Gres, V. Boulay, P. Bongrand, C. Farnarier, and G. Kaplanski The IL-6-Soluble IL-6R{alpha} Autocrine Loop of Endothelial Activation as an Intermediate Between Acute and Chronic Inflammation: an Experimental Model Involving Thrombin J. Immunol., September 15, 2001; 167(6): 3435 - 3442. [Abstract] [Full Text] [PDF]

				V. Marin, C. Farnarier, S. Gres, S. Kaplanski, M. S.-S. Su, C. A. Dinarello, and G. Kaplanski The p38 mitogen-activated protein kinase pathway plays a critical role in thrombin-induced endothelial chemokine production and leukocyte recruitment Blood, August 1, 2001; 98(3): 667 - 673. [Abstract] [Full Text] [PDF]

				S. R. Goth and R. S. Stephens Rapid, Transient Phosphatidylserine Externalization Induced in Host Cells by Infection with Chlamydia spp. Infect. Immun., February 1, 2001; 69(2): 1109 - 1119. [Abstract] [Full Text] [PDF]

				U. Maus, S. Herold, H. Muth, R. Maus, L. Ermert, M. Ermert, N. Weissmann, S. Rosseau, W. Seeger, F. Grimminger, et al. Monocytes recruited into the alveolar air space of mice show a monocytic phenotype but upregulate CD14 Am J Physiol Lung Cell Mol Physiol, January 1, 2001; 280(1): L58 - L68. [Abstract] [Full Text] [PDF]

				E. A. Lidington, D. O. Haskard, and J. C. Mason Induction of decay-accelerating factor by thrombin through a protease-activated receptor 1 and protein kinase C-dependent pathway protects vascular endothelial cells from complement-mediated injury Blood, October 15, 2000; 96(8): 2784 - 2792. [Abstract] [Full Text] [PDF]

				G. J. R. Zaman and E. M. Conway The elusive factor Xa receptor: failure to detect transcripts that correspond to the published sequence of EPR-1 Blood, July 1, 2000; 96(1): 145 - 148. [Abstract] [Full Text] [PDF]

				G. GRANDALIANO, R. MONNO, E. RANIERI, L. GESUALDO, F. P. SCHENA, C. MARTINO, and M. URSI Regenerative and Proinflammatory Effects of Thrombin on Human Proximal Tubular Cells J. Am. Soc. Nephrol., June 1, 2000; 11(6): 1016 - 1025. [Abstract] [Full Text]

				D. Ping, G. Boekhoudt, and J. M. Boss trans-Retinoic Acid Blocks Platelet-derived Growth Factor-BB-induced Expression of the Murine Monocyte Chemoattractant-1 Gene by Blocking the Assembly of a Promoter Proximal Sp1 Binding Site J. Biol. Chem., November 5, 1999; 274(45): 31909 - 31916. [Abstract] [Full Text] [PDF]

				S. R. Coughlin How the protease thrombin talks to cells PNAS, September 28, 1999; 96(20): 11023 - 11027. [Abstract] [Full Text] [PDF]

				K. D. Srivastava and H. I. Magazine Thrombin Receptor Activation Inhibits Monocyte Spreading by Induction of ETB Receptor-Coupled Nitric Oxide Release J. Immunol., November 1, 1998; 161(9): 5039 - 5044. [Abstract] [Full Text] [PDF]

				N. H. M. Senden, T. M. A. A. Jeunhomme, J. W. M. Heemskerk, R. Wagenvoord, C. van't Veer, H. C. Hemker, and W. A. Buurman Factor Xa Induces Cytokine Production and Expression of Adhesion Molecules by Human Umbilical Vein Endothelial Cells J. Immunol., October 15, 1998; 161(8): 4318 - 4324. [Abstract] [Full Text] [PDF]

				G. Kaplanski, V. Marin, M. Fabrigoule, V. Boulay, A.-M. Benoliel, P. Bongrand, S. Kaplanski, and C. Farnarier Thrombin-Activated Human Endothelial Cells Support Monocyte Adhesion In Vitro Following Expression of Intercellular Adhesion Molecule-1 (ICAM-1; CD54) and Vascular Cell Adhesion Molecule-1 (VCAM-1; CD106) Blood, August 15, 1998; 92(4): 1259 - 1267. [Abstract] [Full Text] [PDF]

				O. Dery, C. U. Corvera, M. Steinhoff, and N. W. Bunnett Proteinase-activated receptors: novel mechanisms of signaling by serine proteases Am J Physiol Cell Physiol, June 1, 1998; 274(6): C1429 - C1452. [Abstract] [Full Text] [PDF]

				K. Johnson, Y. Choi, E. DeGroot, I. Samuels, A. Creasey, and L. Aarden Potential Mechanisms for a Proinflammatory Vascular Cytokine Response to Coagulation Activation J. Immunol., May 15, 1998; 160(10): 5130 - 5135. [Abstract] [Full Text] [PDF]

				A. Papapetropoulos, P. Piccardoni, G. Cirino, M. Bucci, R. Sorrentino, C. Cicala, K. Johnson, V. Zachariou, W. C. Sessa, and D. C. Altieri Hypotension and inflammatory cytokine gene expression triggered by factor Xa-nitric oxide signaling PNAS, April 14, 1998; 95(8): 4738 - 4742. [Abstract] [Full Text] [PDF]

				S. R. Coughlin Sol Sherry Lecture in Thrombosis : How Thrombin `Talks' to Cells Molecular Mechanisms and Roles In Vivo Arterioscler. Thromb. Vasc. Biol., April 1, 1998; 18(4): 514 - 518. [Full Text] [PDF]

				F. Wempe, V. Lindner, and H. G. Augustin Basic Fibroblast Growth Factor (bFGF) Regulates the Expression of the CC Chemokine Monocyte Chemoattractant Protein-1 (MCP-1) in Autocrine-Activated Endothelial Cells Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 2471 - 2478. [Abstract] [Full Text]

				V.K. Stark, J.R. Hoch, T.F. Warner, and D.A. Hullett Monocyte Chemotactic Protein-1 Expression Is Associated With the Development of Vein Graft Intimal Hyperplasia Arterioscler. Thromb. Vasc. Biol., August 1, 1997; 17(8): 1614 - 1621. [Abstract] [Full Text]

				F. Li, D. Baykal, C. Horaist, C.-N. Yan, B. N. Carr, G. N. Rao, and M. S. Runge Cloning and Identification of Regulatory Sequences of the Human Thrombin Receptor Gene J. Biol. Chem., October 18, 1996; 271(42): 26320 - 26328. [Abstract] [Full Text] [PDF]

				R. Kranzhofer, S. K. Clinton, K. Ishii, S. R. Coughlin, J. W. Fenton, and P. Libby Thrombin Potently Stimulates Cytokine Production in Human Vascular Smooth Muscle Cells but Not in Mononuclear Phagocytes Circ. Res., August 1, 1996; 79(2): 286 - 294. [Abstract] [Full Text]

				C. Lupu, F. Lupu, U. Dennehy, V. V. Kakkar, and M. F. Scully Thrombin Induces the Redistribution and Acute Release of Tissue Factor Pathway Inhibitor From Specific Granules Within Human Endothelial Cells in Culture Arterioscler. Thromb. Vasc. Biol., November 1, 1995; 15(11): 2055 - 2062. [Abstract] [Full Text]

				U. O. Wenzel, B. Fouqueray, G. Grandaliano, Y.-S. Kim, C. Karamitsos, A. J. Valente, and H. E. Abboud Thrombin Regulates Expression of Monocyte Chemoattractant Protein-1 in Vascular Smooth Muscle Cells Circ. Res., September 1, 1995; 77(3): 503 - 509. [Abstract] [Full Text]