Therapeutic Options for Transfusion Related Acute Lung Injury; the Potential of the G2A Receptor

Michael      A. Ellison; Daniel      R. Ambruso; Christopher      C. Silliman

doi:10.2174/1381612811209023255

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