Complement Activation and the Platelet Storage Le

We will systematically examine whether complement activation plays a significant role in theplatelet storage lesion (PSL). The goals of the project are four-fold: (1) to assess the etiology of PSL bydepleting complement factor 8 from platelet storage plasma; (2) determine if monoclonal antibodiesdirected against C8 or C9 inhibit the PSL; (3) determine if CD59, a naturally occurring inhibitor of theassembly of terminal complement components can attenuate the development of PSL; and (4) based onresults obtained in 1-3, determine whether any of these approaches will arrest the development of PSLin platelet concentrates prepared and stored using FDA approved blood bank procedures. A cleardemonstration of a complement-mediated component in PSL would ultimately lead to Phase II testingof complement inhibiting agents in platelet concentrate preparations and an assessment of plateletsurvival. Accordingly, the Phase I studies, if successful, have a clear connection to Phase II studies.