Platelet-derived microparticles induce polymorphonuclear leukocyte-mediated damage of XXXX pulmonary microvascular endothelial cells.

@entity1 @entity12824 @entity2936 @entity11603 @entity25982 @entity273 @entity358 @entity9536 @entity2071 @entity647
BACKGROUND: Platelets (PLTs) stored at 22  C accumulate microparticles and biologic response modifiers (BRMs) that induce inflammatory reactions in transfusion recipients. However, soluble BRMs are fully diluted in the recipient's blood circulation. The mechanisms by which BRMs exert their effects have not been elucidated. The objectives of this study were to determine the effect of PLT microparticles (PMPs) on polymorphonuclear leukocyte (PMN)-mediated @entity1 pulmonary microvascular endothelial cell (HMVEC) damage and determine the role of soluble @entity2936 ligand (sCD40L). STUDY DESIGN AND METHODS: PMPs were isolated from apheresis PLT concentrates. We used a two-insult in vitro model of @entity358 to investigate the effects of @entity25982 and sCD40L and role of @entity12824 , an inhibitor of PMN respiratory burst. Their priming activities were measured using @entity273 production. The expression of @entity2071 ( @entity2071 ) and integrin aM ( @entity9536 ) were also determined. RESULTS: Lipopolysaccharide (LPS)-activated @entity358 and PMN respiratory burst depend on the presence of @entity25982 and the concentration of sCD40L. @entity25982 -induced PMN-mediated @entity358 was significantly reduced by @entity12824 -treated PMNs (p   <   0.05). The surface expression of @entity2071 on HMVEC was increased by LPS stimulation. The expression of @entity9536 on PMNs was increased by @entity25982 priming. Blocking @entity2071 with a monoclonal antibody (MoAb) @entity2071 significantly reduced @entity358 (p   <   0.05). The treatment of endothelial cells but not PMN with a MoAb targeting @entity2936 failed to prevent the @entity358 caused by PMPs (p   >   0.05). CONCLUSION: PMPs carry a concentrated @entity11603 signal, promote PMN-mediated @entity358 , and may affect the development of transfusion-related @entity647 .
