Early storage lesions in apheresis platelets are induced by the activation of the integrin αIIbβ₃ and focal adhesion signaling pathways.
Production and storage of platelet concentrates (PC) induce protein changes in platelets leading to impaired platelet function. This study aimed to identify signaling pathways involved in the development of early platelet storage lesions in apheresis-PCs stored in plasma or additive solution (PAS). Apheresis-PCs from four donors were stored in plasma or in PAS at 22°C (n=4 each). Platelets were analyzed at day 0 (production day) and after 1, 6 and 9 days of storage. Platelet response to agonists (TRAP, collagen, ADP) and to hypotonic shock decreased, CD62P expression increased in both storage media over time. Using DIGE 1550 protein spots were monitored and compared to baseline values at day 0. Platelets in plasma displayed changes in 352 spots (166/day 1, 263/day 6 and 201/day 9); in PAS 325 spots changed (202/day 1, 221/day 6, 200/day 9). LC-ESI-MS/MS analysis of 405 platelet proteins revealed 32 proteins changed during storage in plasma (9/day 1, 15/day 6 and 26/day 9) and 28 in PAS (5/day 1, 20/day 6, 26/day 9). Ingenuity pathway analysis found integrin-αII(b)β(3) and focal adhesion signaling pathways involved in early alterations, being confirmed by Western blotting. Corresponding mRNAs in platelets were identified by next generation sequencing for 84 changed proteins. Integrin-αII(b)β(3) and focal adhesion signaling cause irreversible early storage lesions in apheresis platelets. This article is part of a Special Issue entitled: Integrated omics.
Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Germany. thomas.thiele@uni-greifswald.de
Thomas
T
Thiele
Cristina
C
Iuga
Susann
S
Janetzky
Hansjorg
H
Schwertz
Manuela
M
Gesell Salazar
Birgit
B
Fürll
Uwe
U
Völker
Andreas
A
Greinacher
Leif
L
Steil
D000328:Adult; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D001793:Blood Preservation; D001798:Blood Proteins / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D010983:Plateletpheresis; D015398:Signal Transduction; D013997:Time Factors
D001798:Blood Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex