Random aggregates in newly produced platelet units are associated with platelet activation and release of the immunomodulatory factors sCD40L and RANTES

Abstract

Our data indicate that random occurrence of aggregates may lead to higher activation level and increased release of immunomodulatory factors from the PLTs.

In vitro affinity reduction of biologic response modifiers from production buffy coat platelets exposed to recombinant protein receptors

“…33 Also the expression level of the GPIb-IX-V complex 34,35 and maintenance of the PECAM-1 (CD31) levels of filtered PLTs 36,37 strengthens the conclusion that filtration does not adversely affect PLT quality. Moreover, our results on the filtered PLTs seem to agree with the functional integrity of the OrbiSac-produced PLTs proven earlier in a series of in vitro assays 2,22,23,29,30,37 and more than 10 years of clinical experience including more than 1.5 million units produced worldwide.…”

“…Supporting such a hypothesis, several BRMs have recently been linked to transfusion reactions, 1,5,7,8,12,43 while concentrations of several cytokines increase in the bag with storage times, suggesting de novo production or release from intracellular sites. [1][2][3]44 Thus it is possible that the depletion of BRMs may contribute to prolong PLTs shelf life and/or reduce transfusion reactions. Such an effect remains to be demonstrated, but with the technology described in this study it is feasible.…”

“…I t is well known that currently used protocols for the preparation and storage of platelet (PLT) concentrates from donor blood induce the release of biologic response modifiers (BRMs). [1][2][3] Consisting of both cytokines and other biomolecules, these BRMs are thought to activate autocrine and paracrine pathways to influence key cellular functions of both donor and recipient cells. [4][5][6][7][8] Of importance, recent data link BRMs to adverse transfusion reactions after human PLT concentrate therapy.…”

Pathogen inactivation of double‐dose buffy‐coat platelet concentrates photochemically treated with amotosalen and UVA light: preservation of in vitro function

“…mlp Acquisition and mlp Analysis software packages (Beckman Coulter) were used for data acquisition and analysis, respectively. All methods including staining were performed as described . All sCD40L concentrations were determined with commercial ELISA kits (Quantikine, CD40 Ligand Immunoassay DCDL40) in accordance with the manufacturer's (R&D Systems Inc., Minneapolis, MN, USA) recommendations.…”

Platelet concentrate supernatants alter endothelial cell mRNA and protein expression patterns as a function of storage length

“…The induced activation of the modeled vascular endothelium resulted in the release of cytokines/chemokines and the modulation of the surface expression of adhesion molecules, specifically intercellular adhesion molecule (ICAM)‐1 . Supernatants from certain stored PCs, both involved or not involved in SARs, create proinflammatory conditions as was shown consistently in a large number of investigations both by us and others . However, to date no in‐depth investigation has been performed to determine how pathogenic PC supernatants (BRMs) can alter EC functions.…”