Abstract
Priming of polymorphonuclear leukocytes (PMNs) enhances their adhesion to endothelium, the release of their granule content and their production of reactive oxygen species. These effects are etiological in transfusion related acute lung injury (TRALI) and many clinically important mediators of TRALI prime PMNs. A priming activity that develops over time in stored blood products has been shown to be due to the accumulation of lysophospatidylcholines (lyso-PCs) and has been found to be related clinically to TRALI. Lyso- PCs prime PMNs activating the G2A receptor and several inhibitors of this receptor, which could potentially be therapeutic in TRALI, have been identified. Recent work has described early steps in the signaling from the G2A receptor which has revealed potential targets for novel antagonists of lyso-PC mediated priming via G2A. Additionally, characterization of the process by which lyso-PCs are generated in stored blood products could allow development of inhibitors and additive solutions to block their formation in the first place.
Keywords: Transfusion-related acute lung injury, lysophospholipid, lysophosphatidylcholine, G2A receptor, G-protein coupled receptor, clathrin-mediated endocytosis, polymorphonuclear leukocytes (PMNs), blood products, inhibitors, additive solutions
Current Pharmaceutical Design
Title:Therapeutic Options for Transfusion Related Acute Lung Injury; the Potential of the G2A Receptor
Volume: 18 Issue: 22
Author(s): Michael A. Ellison, Daniel R. Ambruso and Christopher C. Silliman
Affiliation:
Keywords: Transfusion-related acute lung injury, lysophospholipid, lysophosphatidylcholine, G2A receptor, G-protein coupled receptor, clathrin-mediated endocytosis, polymorphonuclear leukocytes (PMNs), blood products, inhibitors, additive solutions
Abstract: Priming of polymorphonuclear leukocytes (PMNs) enhances their adhesion to endothelium, the release of their granule content and their production of reactive oxygen species. These effects are etiological in transfusion related acute lung injury (TRALI) and many clinically important mediators of TRALI prime PMNs. A priming activity that develops over time in stored blood products has been shown to be due to the accumulation of lysophospatidylcholines (lyso-PCs) and has been found to be related clinically to TRALI. Lyso- PCs prime PMNs activating the G2A receptor and several inhibitors of this receptor, which could potentially be therapeutic in TRALI, have been identified. Recent work has described early steps in the signaling from the G2A receptor which has revealed potential targets for novel antagonists of lyso-PC mediated priming via G2A. Additionally, characterization of the process by which lyso-PCs are generated in stored blood products could allow development of inhibitors and additive solutions to block their formation in the first place.
Export Options
About this article
Cite this article as:
A. Ellison Michael, R. Ambruso Daniel and C. Silliman Christopher, Therapeutic Options for Transfusion Related Acute Lung Injury; the Potential of the G2A Receptor, Current Pharmaceutical Design 2012; 18 (22) . https://dx.doi.org/10.2174/1381612811209023255
DOI https://dx.doi.org/10.2174/1381612811209023255 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- 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
-
Microdialysis in Drug Discovery
Current Drug Discovery Technologies The Kidney and the Sympathetic System: A Short Review
Current Clinical Pharmacology Heart Failure Models: Traditional and Novel Therapy
Current Vascular Pharmacology Neuroleptic Malignant Syndrome: A Review from a Clinically Oriented Perspective
Current Neuropharmacology Impact of Aging on the Angiogenic Potential of the Myocardium: Implications for Angiogenic Therapies with Emphasis on Sirtuin Agonists
Recent Patents on Cardiovascular Drug Discovery Advances in the Synthesis of Calystegines and Related Products and their Biochemical Properties
Mini-Reviews in Medicinal Chemistry Nursing Assessment, Education, and Care of Extremely Premature Neonates with Patent Ductus Arteriosus
Current Pediatric Reviews Perception of Symptoms in Hypertensive Patients and the Relevance to the Application of Anti- Hypertensive Drug Therapy
Current Pharmaceutical Design Hydrophilic Dual Vitamin E-Like Antioxidants as Modulators of Inflammatory Response in Low-Flow States and Impaired Wound Healing
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Statins in Bacteremia, Sepsis and Pneumonia: Have We Found the Holy Grail?
Recent Patents on Inflammation & Allergy Drug Discovery Natural or Plant Products for the Treatment of Neurological Disorders: Current Knowledge
Current Drug Metabolism Pulmonary Arterial Hypertension: Need to Treat
Inflammation & Allergy - Drug Targets (Discontinued) Nitric Oxide and Dietary Factors: Part V Summary/Conclusion and References
Vascular Disease Prevention (Discontinued) Immunosuppression in Liver Transplantation
Current Drug Targets Adoptive Immunotherapy for B-cell Malignancies Using CD19- Targeted Chimeric Antigen Receptor T-Cells: A Systematic Review of Efficacy and Safety
Current Medicinal Chemistry Amniotic Fluid Embolism: Moving Diagnosis Through the Time. From the Mechanical Pulmonary Vascular Occlusion Until An Immuno - Inflammatory Pathogenesis?
Current Pharmaceutical Biotechnology Pharmacological Treatment of Hypertension in Pregnancy
Current Pharmaceutical Design Context-Dependency of Relations Between Cardiovascular Phenotypes and Genes Involved in Sodium Homeostasis: Findings from the European Project on Genes in Hypertension
Current Hypertension Reviews Vasodilator Effects of Bis-Dihydropyridines Structurally Related to Nifedipine
Medicinal Chemistry L-Arginine Availability as a Pathological Mechanism in Essential Hypertension, Chronic Renal and Heart Failure
Vascular Disease Prevention (Discontinued)