Abstract
The urokinase plasminogen activator (uPA) and its receptor (uPAR) provide a cell surface integrated multimolecular complex that exerts pleiotropic functions influencing the development of inflammatory, immune, coagulation and fibrinolytic responses. Here we review the evidences indicating a role of the uPA/uPAR system in the regulation of the innate immune system in the inflammation process, of the adaptive immune response, as well as the role of fibrin and fibrin degradation products at the cross-road between coagulation and inflammation. Comparative studies have clearly highlighted the notion that coagulation and immunity are co-regulated and intertwined. The implication is that the vertebrate blood clotting system is evolutionarily by product of the innate immune system, where the blood clotting proteases have diverged from those comprising the complement system. Differences have emerged gradually, as shown by the acquisition of unique protein structures, such as kringle domains and gla (glutammic acid) domains, in order to comply with the increasingly complex vertebrate systems and to defend higher organisms against a range of infections and injuries. Plasminogen activation also controls the formation of complement anaphylotoxins (responsibe for vasodilatation, increase of venular permeability and leukocyte chemotaxis) and of bradykinin (which accounts for vasodilatation, increase of venular permeability and pain) by regulating the plasma contact system. The urokinase plasminogen activator and its cellular receptor, expressed on the surface of human leukocytes, provide a functional unit that, by regulating interaction of leukocytes with extracellular matrix, as well as its degradation, is critical for the migration of leukocytes and for their movement in the damaged tissues.
Keywords: uPAR, uPA, inflammation, immunity, coagulation, contact system, plasminogen, vitronectin, bacterial endotoxins, epidermal growth factor, immune system, amino acids, phagocytosis, apoptosis, pro-inflammatory activity
Current Pharmaceutical Design
Title: The Urokinase Receptor System, A Key Regulator at the Intersection between Inflammation, Immunity, and Coagulation
Volume: 17 Issue: 19
Author(s): Mario Del Rosso, Francesca Margheri, Simona Serrati, Anastasia Chilla, Anna Laurenzana and Gabriella Fibbi
Affiliation:
Keywords: uPAR, uPA, inflammation, immunity, coagulation, contact system, plasminogen, vitronectin, bacterial endotoxins, epidermal growth factor, immune system, amino acids, phagocytosis, apoptosis, pro-inflammatory activity
Abstract: The urokinase plasminogen activator (uPA) and its receptor (uPAR) provide a cell surface integrated multimolecular complex that exerts pleiotropic functions influencing the development of inflammatory, immune, coagulation and fibrinolytic responses. Here we review the evidences indicating a role of the uPA/uPAR system in the regulation of the innate immune system in the inflammation process, of the adaptive immune response, as well as the role of fibrin and fibrin degradation products at the cross-road between coagulation and inflammation. Comparative studies have clearly highlighted the notion that coagulation and immunity are co-regulated and intertwined. The implication is that the vertebrate blood clotting system is evolutionarily by product of the innate immune system, where the blood clotting proteases have diverged from those comprising the complement system. Differences have emerged gradually, as shown by the acquisition of unique protein structures, such as kringle domains and gla (glutammic acid) domains, in order to comply with the increasingly complex vertebrate systems and to defend higher organisms against a range of infections and injuries. Plasminogen activation also controls the formation of complement anaphylotoxins (responsibe for vasodilatation, increase of venular permeability and leukocyte chemotaxis) and of bradykinin (which accounts for vasodilatation, increase of venular permeability and pain) by regulating the plasma contact system. The urokinase plasminogen activator and its cellular receptor, expressed on the surface of human leukocytes, provide a functional unit that, by regulating interaction of leukocytes with extracellular matrix, as well as its degradation, is critical for the migration of leukocytes and for their movement in the damaged tissues.
Export Options
About this article
Cite this article as:
Rosso Mario Del, Margheri Francesca, Serrati Simona, Chilla Anastasia, Laurenzana Anna and Fibbi Gabriella, The Urokinase Receptor System, A Key Regulator at the Intersection between Inflammation, Immunity, and Coagulation, Current Pharmaceutical Design 2011; 17 (19) . https://dx.doi.org/10.2174/138161211796718189
DOI https://dx.doi.org/10.2174/138161211796718189 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Polypharmacology of <i>Aconitum</i> and <i>Delphinium</i> sp. Diterpene Alka loids: Antiarrhythmic, Analgesic and Anti-Inflammatory Effects
Mini-Reviews in Organic Chemistry Molecular Effects of L-dopa Therapy in Parkinson’s Disease
Current Genomics Interaction Between Bone and Muscle in Older Persons with Mobility Limitations
Current Pharmaceutical Design Non-Analgesic Effects of Opioids: Neuroprotection in the Retina
Current Pharmaceutical Design Small Molecules in Treatment of Sepsis
Current Drug Targets Cardio-Vascular Risks Associated with Clozapine Treatment
Current Psychiatry Reviews Lemont B. Kier: A Bibliometric Exploration of his Scientific Production and its Use
Current Computer-Aided Drug Design Sildenafil is Well Tolerated by Erectile Dysfunction Patients Taking Antihypertensive Medications, Including Those on Multidrug Regimens
Current Drug Safety Perspectives on Brain-Targeting Drug Delivery Systems
Current Pharmaceutical Biotechnology Use of Medication in Coronary Imaging by CT
Current Medical Imaging Central Nervous System Abnormalities in Fibromyalgia and Chronic Fatigue Syndrome: New Concepts in Treatment
Current Pharmaceutical Design Initiation of Dialysis: A Mini-Review of a Changing Paradigm
Cardiovascular & Hematological Disorders-Drug Targets Clinical Immunotherapy of B-Cell Malignancy Using CD19-Targeted CAR T-Cells
Current Gene Therapy COXIBs, CINODs and H2S-Releasing NSAIDs: Current Perspectives in the Development of Safer Non Steroidal Anti-Inflammatory Drugs
Current Medicinal Chemistry HCN Pacemaker Channels and Pain: A Drug Discovery Perspective
Current Pharmaceutical Design The Therapeutic Potential and Usage Patterns of Cannabinoids in People with Spinal Cord Injuries: A Systematic Review
Current Neuropharmacology Optimal Sedation for the Ventilation of Critically Ill Patients
Current Respiratory Medicine Reviews Editorial: Perioperative Pharmacological Management: From Prescription Medications to Dietary Supplements
Current Clinical Pharmacology Molecular and Cellular Mechanisms in the Pathophysiology of Severe Head Injury
Current Pharmaceutical Design Molecule of the Month
Current Topics in Medicinal Chemistry