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.
