A novel biologic activity of thrombin: stimulation of monocyte chemotactic protein production

Thrombin is a serine protease that is released at sites of vascular injury and exerts a variety of biologic effects on different cell types. Thrombin is postulated to play a role in the pathogenesis of a number of diseases including atherosclerosis, since it activates vascular smooth muscle and endothelial cells. Thrombin mediates these effects through a specific receptor that is upregulated in vascular cells in atherosclerosis. Atherosclerosis and glomerulosclerosis are characterized by the presence of monocyte-macrophages in the lesions. Monocyte chemotactic protein (MCP-1) is believed to be an important mediator of monocyte recruitment to the tissue and can be induced in a broad variety of cells including mesangial cells. We studied the effect of thrombin on MCP-1 production and gene expression in well- characterized human mesangial cells, vascular pericytes that play a central role in fibrosis of the glomerular microvascular bed. alpha thrombin stimulates MCP-1 production and gene expression in mesangial cells in a dose- and time-dependent manner. Experiments with diisopropylfluorophosphate thrombin and gamma thrombin demonstrate that this thrombin effect requires both receptor binding as well as catalytic activity, features consistent with the known properties of the recently characterized and cloned thrombin receptor. Moreover, a human thrombin receptor activating peptide (TRAP1-7) also stimulates MCP-1 production. Northern blot analysis demonstrated that mesangial cells express an mRNA transcript that hybridizes with labeled human thrombin receptor cDNA. These data describe a novel biologic activity of thrombin and suggest an additional mechanism by which this coagulation factor may participate in the progression of glomerulosclerosis, and by analogy, atherosclerosis.

• Publication year

  1994

• Venue

  Journal of Experimental Medicine

• Publication date

  1994-05-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/JEM.179.5.1737PMID 8163952PMCID 2191479
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor.

  1993influential reference
• Cultured human liver fat-storing cells produce monocyte chemotactic protein-1. Regulation by proinflammatory cytokines.

  1993cited by this paper
• LDL stimulates mesangial fibronectin production and chemoattractant expression.

  1993cited by this paper
• Regulation of monocyte chemoattractant protein-1 and macrophage colony-stimulating factor-1 by IFN-gamma, tumor necrosis factor-alpha, IgG aggregates, and cAMP in mouse mesangial cells.

  1993cited by this paper
• Glomerular cell proliferation and PDGF expression precede glomerulosclerosis in the remnant kidney model.

  1992cited by this paper
• Thrombin receptor expression in normal and atherosclerotic human arteries.

  1992cited by this paper
• Thrombin stimulates PDGF production and monocyte adhesion through distinct intracellular pathways in human endothelial cells.

  1992cited by this paper
• Cytokine-induced production of monocyte chemoattractant protein-1 by cultured human mesangial cells.

  1992cited by this paper
• T cells and macrophages and their role in renal injury.

  1992cited by this paper
• Elevated expression of monocyte chemoattractant protein 1 by vascular smooth muscle cells in hypercholesterolemic primates.

  1992cited by this paper
• Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions.

  1991cited by this paper
• Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation.

  1991influential reference
• Monocyte chemoattractant protein-1 in human atheromatous plaques.

  1991cited by this paper
• Human monocyte chemoattractant protein-1 (MCP-1).

  1990cited by this paper
• A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas

  1990cited by this paper
• Mitogenic signals for thrombin in mesangial cells: regulation of phospholipase C and PDGF genes.

  1989cited by this paper
• Mesangial cells express PDGF mRNAs and proliferate in response to PDGF.

  1988cited by this paper
• Focal and segmental glomerulosclerosis: analogies to atherosclerosis.

  1988cited by this paper
• Secretory products of macrophages.

  1987cited by this paper
• Two growth factor signalling pathways in fibroblasts distinguished by pertussis toxin

  1987cited by this paper
• Thrombin stimulates c-sis gene expression in microvascular endothelial cells.

  1986cited by this paper
• Thrombin‐Cellular Interactions

  1986cited by this paper
• Alpha-thrombin induces release of platelet-derived growth factor-like molecule(s) by cultured human endothelial cells

  1986cited by this paper
• Primary glomerular diseases (primary glomerulopathies).

  1986cited by this paper
• The detection of monocytes in human glomerulonephritis.

  1985cited by this paper
• Activation of coagulation pathways and fibrin deposition in human glomerulonephritis.

  1985cited by this paper
• Chemotactic response of monocytes to thrombin

  1983cited by this paper
• Cell-mediated immunity in glomerulonephritis.

  1981cited by this paper
• The effect of defibrination on macrophage participation in rabbit nephrotoxic nephritis: studies using glomerular culture and electronmicroscopy.

  1979cited by this paper

• Prospective study of cesarean scar pregnancy associated with increased MCP-1 and cholesterol synthesis

  2025cites this paper
• Thrombin: A Pivotal Player in Hemostasis and Beyond

  2021cites this paper
• Thrombin impairs the angiogenic activity of extravillous trophoblast cells via monocyte chemotactic protein-1 (MCP-1): A possible link with preeclampsia.

  2021cites this paper
• Mechanisms Involved in Childhood Obesity-Related Bone Fragility

  2019cites this paper
• Tranexamic acid blocks the thrombin-mediated delay of epidermal permeability barrier recovery induced by the cedar pollen allergen, Cry j1

  2018cites this paper
• Activation of nuclear factor-KB correlates with MCP-1 expression by human mesangial cells

  2015cites this paper
• Recombinant human factor VIIa for alveolar hemorrhage following allogeneic stem cell transplantation.

  2014cites this paper
• Cellular signaling crosstalk between multiple receptors for investigation of pathophysiology in multifactorial diseases--what is clinically-relevant crosstalk?

  2013cites this paper
• Alteración de la placentación profunda en la preeclampsia

  2012cites this paper
• Exogenous Thrombin Delivery Promotes Collateral Capillary Arterialization and Tissue Reperfusion in the Murine Spinotrapezius Muscle Ischemia Model

  2012cites this paper
• Roles of fibrin deposition and protease activated receptor-1 in renal cytokine/chemokine production and inflammatory cell infiltration in rats of different ages

  2011cites this paper
• A guide towards pre-pregnancy management of defective implantation and placentation.

  2011cites this paper
• Biodegradable nanocomposite microparticles as drug delivering injectable cell scaffolds.

  2011influential citation
• Monocyte chemoattractant protein 1 mediates glomerular macrophage infiltration in anti-GBM Ab GN WINs 0

  2010cites this paper
• Renoprotective effect of Kangen-karyu on the development of diabetic nephropathy in type 2 diabetic db/db mice

  2010cites this paper
• Fisiopatología de la aterosclerosis

  2010cites this paper
• Concentration dependent dual effect of thrombin in endothelial cells via Par‐1 and Pi3 Kinase

  2009cites this paper
• Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche.

  2009cites this paper
• Protease-activated receptor 1 activation is necessary for monocyte chemoattractant protein 1–dependent leukocyte recruitment in vivo

  2008cites this paper
• Defective implantation and placentation: laying the blueprint for pregnancy complications.

  2007cites this paper
• Thrombin regulates monocyte chemoattractant protein-1 expression in human first trimester and term decidual cells.

  2007cites this paper
• CHAPTER 42 – Tumor Growth and Metastasis

  2007cites this paper
• Role of Ca(2+)influx in tissue factor expression in monocyte adhesion to endothelial cells.

  2007cites this paper
• Defective implantation and placentation: laying the blueprint for pregnancy complications.

  2006cites this paper
• Cytokines in atherosclerosis: pathogenic and regulatory pathways.

  2006cites this paper
• Coagulopathy and inflammation in neonatal heart surgery: mechanisms and strategies.

  2006cites this paper
• Novel aspects of renal tubulointerstitial fibrosis

  2006cites this paper
• Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response.

  2005cites this paper
• The contribution of the endothelium to the development of coagulation disorders that characterize Ebola hemorrhagic fever in primates

  2005cites this paper
• Coagulation cascade activation causes CC chemokine receptor-2 gene expression and mononuclear cell activation in hemodialysis patients.

  2005cites this paper
• Extracellular proteases of Acanthamoeba castellanii (encephalitis isolate belonging to T1 genotype) contribute to increased permeability in an in vitro model of the human blood-brain barrier.

  2005cites this paper
• A cross-talk between the blood coagulation system, and inflammatory and immune systems

  2004cites this paper
• The pathogenesis of Acanthamoeba infections: current statusand future implications

  2004cites this paper
• The Blood Platelet as a Model for Regulating Blood Coagulation on Cell Surfaces and Its Consequences

  2004cites this paper
• Application of bioencapsulated proteinases and peptides for wound gealing

  2004cites this paper
• Thrombin and Phenotypic Modulation of the Endothelium

  2004cites this paper
• Role of mesangial Factor V expression in crescent formation in rat experimental mesangioproliferative glomerulonephritis

  2004cites this paper
• Macrophage Migration Inhibitory Factor Is Induced by Thrombin and Factor Xa in Endothelial Cells*

  2004cites this paper
• jun-N-terminal kinase regulates thrombin-induced PAI-1 gene expression in proximal tubular epithelial cells.

  2004cites this paper
• Inflammatory response to cardiopulmonary bypass.

  2003cites this paper
• Activation of Coagulation by Administration of Recombinant Factor VIIa Elicits Interleukin 6 (IL-6) and IL-8 Release in Healthy Human Subjects

  2003cites this paper
• Regulation of protease-activated receptor-1 in mononuclear cells by neutrophil proteases.

  2003cites this paper
• A novel chemokine, Leukotactin-1, induces chemotaxis, pro-atherogenic cytokines, and tissue factor expression in atherosclerosis.

  2002cites this paper
• Differential Expression of Mcp-1 and Its Receptor CCR2 in Glucose Primed Human Mesangial Cells

  2002cites this paper
• Human corneal epithelial cells express functional PAR-1 and PAR-2.

  2002cites this paper
• Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo.

  2002cites this paper
• Thrombin receptor antagonists; recent advances in PAR-1 antagonist development.

  2002cites this paper
• Anticoagulant factor concentrates in disseminated intravascular coagulation: rationale for use and clinical experience.

  2001cites this paper
• Interface Between Inflammation and Coagulation

  2001cites this paper
• Thrombin regulates chemokine induction during human retinal pigment epithelial cell/monocyte interaction.

  2001cites this paper
• Regulation of nuclear factor κB activation by G‐protein‐coupled receptors

  2001cites this paper
• Anticoagulant Factor Concentrates in Disseminated Intravascular Coagulation: Rationale for Use and Clinical Experience

  2001cites this paper
• Activated platelets and endothelial cell interaction with neutrophils under flow conditions.

  2001cites this paper
• Activated coagulation factor X: a novel mitogenic stimulus for human mesangial cells.

  2001cites this paper
• The p38 mitogen-activated protein kinase pathway plays a critical role in thrombin-induced endothelial chemokine production and leukocyte recruitment.

  2001cites this paper
• Immobilized Thrombin Receptor Agonist Peptide Accelerates Wound Healing in Mice

  2001cites this paper
• The IL-6-Soluble IL-6Rα Autocrine Loop of Endothelial Activation as an Intermediate Between Acute and Chronic Inflammation: an Experimental Model Involving Thrombin

  2001influential citation
• Tissue factor, plasminogen activator inhibitor-1, and thrombin receptor expression in human crescentic glomerulonephritis.

  2000cites this paper
• Regenerative and proinflammatory effects of thrombin on human proximal tubular cells.

  2000cites this paper
• Distribution and potential biologic function of the thrombin receptor PAR-1 on human keratinocytes

  2000cites this paper
• Receptor Mediated Endocytosis by Mesangial Cells Modulates Transmigration of Macrophages

  2000cites this paper
• Protease-Activated Receptor 1 Mediates Thrombin-Dependent, Cell-Mediated Renal Inflammation in Crescentic Glomerulonephritis

  2000cites this paper
• Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy.

  2000cites this paper
• Chemokines, chemokine receptors, and renal disease: from basic science to pathophysiologic and therapeutic studies.

  2000cites this paper
• Thrombin and factor Xa enhance neutrophil chemoattractant production after ischemia/reperfusion in the rat liver.

  2000cites this paper
• Thrombin Inhibitor Ameliorates Secondary Damage in Rat Brain Injury: Suppression of Inflammatory Cells and Vimentin-Positive Astrocytes

  2000influential citation
• Chemokine and chemokine receptor expression in a novel human mesangial cell line.

  1999cites this paper
• A Synthetic Selective Inhibitor of Factor Xa, DX-9065a, Reduces Monocyte Chemoattractant Protein-1 Expression After Ischemia-Reperfusion Injury in Rat Liver

  1999cites this paper
• Survey The MCP/eotaxin subfamily of CC chemokines

  1999cites this paper
• Hypertensive vascular disease and inflammation: mechanical and humoral mechanisms.

  1999cites this paper
• Chemokines, Renal Disease, and HIV Infection

  1999cites this paper
• Injury‐induced gelatinase and thrombin‐like activities in regenerating and nonregenerating nervous systems

  1999cites this paper
• Hypertensive vascular disease and inflammation: Mechanical and humoral mechanisms

  1999cites this paper
• Identification of a unique glomerular factor X activator in murine lupus nephritis.

  1999cites this paper
• Thrombin: A Novel Renal Growth Factor

  1999cites this paper
• The MCP/eotaxin subfamily of CC chemokines.

  1999cites this paper
• Chemotactic factors and renal inflammation.

  1998cites this paper
• Proteinase-activated receptors: novel mechanisms of signaling by serine proteases.

  1998cites this paper
• Activation Vascular Cytokine Response to Coagulation Potential Mechanisms for a Proinflammatory Creasey and Lucien

  1998cites this paper
• Shiga toxin 1 elicits diverse biologic responses in mesangial cells.

  1998cites this paper
• Matrix-Mesangial Cell Interaction Modulates Migration of Macrophages

  1998cites this paper
• Dust mite proteolytic allergens induce cytokine release from cultured airway epithelium.

  1998cites this paper
• Potential mechanisms for a proinflammatory vascular cytokine response to coagulation activation.

  1998cites this paper
• Dual Regulation of Ligand Binding by CD11b I Domain

  1998cites this paper
• Novel anticoagulants based on inhibition of the factor VIIa/tissue factor pathway.

  1998cites this paper
• Requirement for binding of catalytically active factor VIIa in tissue factor-dependent experimental metastasis.

  1998cites this paper
• 抗トロンビン剤-アルガトロバン-の脳損傷に対する治療効果

  1998cites this paper
• Epithelium Cytokine Release from Cultured Airway Dust Mite Proteolytic Allergens Induce

  1998cites this paper
• Progression of renal damage in human glomerulonephritides: is there sleight of hand in winning the game?

  1997cites this paper
• Vascular thrombin receptor regulation in hypertensive rats.

  1997cites this paper
• Chemokine production by human vascular smooth muscle cells: modulation by IL‐13

  1997cites this paper
• Renal vascular effects of cytokines.

  1997cites this paper
• Activation-dependent Exposure of the Inter-EGF Sequence Leu83-Leu88 in Factor Xa Mediates Ligand Binding to Effector Cell Protease Receptor-1*

  1997cites this paper
• Lymphocyte-derived cytokines induce sequential expression of monocyte- and T cell-specific chemokines in human mesangial cells.

  1997cites this paper
• The c-kit ligand stem cell factor and anti-IgE promote expression of monocyte chemoattractant protein-1 in human lung mast cells.

  1997cites this paper
• Effects of leflunomide and deoxyspergualin in the guinea pig-->rat cardiac model of delayed xenograft rejection: suppression of B cell and C-C chemokine responses but not induction of macrophage lectin.

  1997cites this paper
• Thrombin induces endothelial type II activation in vitro: IL-1 and TNF-alpha-independent IL-8 secretion and E-selectin expression.

  1997cites this paper
• Thrombin receptor: a novel target for antiplatelet drug development.

  1997cites this paper
• Factor Xa as an interface between coagulation and inflammation. Molecular mimicry of factor Xa association with effector cell protease receptor-1 induces acute inflammation in vivo.

  1997cites this paper
• Platelet receptors : The thrombin receptor

  1997cites this paper