title: Platelet-derived microparticles induce polymorphonuclear leukocyte-mediated damage of human pulmonary microvascular endothelial cells.
abstract: 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 human pulmonary microvascular endothelial cell (HMVEC) damage and determine the role of soluble CD40 ligand (sCD40L).
  
  
  METHODS
  PMPs were isolated from apheresis PLT concentrates. We used a two-insult in vitro model of HMVEC damage to investigate the effects of PMP and sCD40L and role of apocynin, an inhibitor of PMN respiratory burst. Their priming activities were measured using hydrogen peroxide production. The expression of intercellular cell adhesion molecule-1 (ICAM-1) and integrin αM (CD11b) were also determined.
  
  
  RESULTS
  Lipopolysaccharide (LPS)-activated HMVEC damage and PMN respiratory burst depend on the presence of PMP and the concentration of sCD40L. PMP-induced PMN-mediated HMVEC damage was significantly reduced by apocynin-treated PMNs (p < 0.05). The surface expression of ICAM-1 on HMVEC was increased by LPS stimulation. The expression of CD11b on PMNs was increased by PMP priming. Blocking ICAM-1 with a monoclonal antibody (MoAb) CD54 significantly reduced HMVEC damage (p < 0.05). The treatment of endothelial cells but not PMN with a MoAb targeting CD40 failed to prevent the HMVEC damage caused by PMPs (p > 0.05).
  
  
  CONCLUSIONS
  PMPs carry a concentrated CD40L signal, promote PMN-mediated HMVEC damage, and may affect the development of transfusion-related acute lung injury.
authors.affiliation: Shanghai Blood Center, Shanghai, China.
authors.forename: Ru Feng
authors.initials: RF
authors.lastname: Xie
authors.affiliation: The Institute of Life Science, East China Normal University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.affiliation: Huashan Hospital, Shanghai, China.
authors.forename: Zhi Cheng
authors.initials: ZC
authors.lastname: Wang
authors.affiliation: Shanghai Blood Center, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Shanghai Blood Center, Shanghai, China.
authors.forename: Yi Ming
authors.initials: YM
authors.lastname: Yang
authors.affiliation: Shanghai Blood Center, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: Shanghai Blood Center, Shanghai, China.
authors.forename: Hua Hua
authors.initials: HH
authors.lastname: Fan
authors.affiliation: Shanghai Blood Center, Shanghai, China.
authors.forename: Yong Ming
authors.initials: YM
authors.lastname: Zhu
mesh_terms: D055371:Acute Lung Injury / Q000628:therapy; D055252:Cell-Derived Microparticles / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000166:cytology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides