title: Microparticles from stored red blood cells activate neutrophils and cause lung injury after hemorrhage and resuscitation.
abstract: BACKGROUND
  Transfusion of stored blood is associated with increased complications. Microparticles (MPs) are small vesicles released from RBCs that can induce cellular dysfunction, but the role of RBC-derived MPs in resuscitation from hemorrhagic shock is unknown. In the current study, we examined the effects of RBC-derived MPs on the host response to hemorrhage and resuscitation.
  
  
  METHODS
  MPs were isolated from murine packed RBC units, quantified using flow cytometry, and injected into healthy mice. Separate groups of mice underwent hemorrhage and resuscitation with and without packed RBC-derived MPs. Lungs were harvested for histology and neutrophil accumulation and assessed by myeloperoxidase content. Human neutrophils were treated with human RBC-derived MPs and CD11b expression, superoxide production, and phagocytic activity were determined.
  
  
  RESULTS
  Stored murine packed RBC units contained increased numbers of RBC-derived MPs compared with fresh units. Hemorrhaged mice resuscitated with MPs demonstrated substantially increased pulmonary neutrophil accumulation and altered lung histology compared with mice resuscitated without MPs. Intravenous injection of MPs into normal mice resulted in neutrophil priming, evidenced by increased neutrophil CD11b expression. Human neutrophils treated with RBC-derived MPs demonstrated increased CD11b expression, increased superoxide production, and enhanced phagocytic ability compared with untreated neutrophils.
  
  
  CONCLUSIONS
  Stored packed RBC units contain increased numbers of RBC-derived MPs. These MPs appear to contribute to neutrophil priming and activation. The presence of MPs in stored units can be associated with adverse effects, including lung injury, after transfusion.
authors.affiliation: Department of Surgery, University of Cincinnati, Cincinnati, OH 45267-0558, USA.
authors.forename: Ritha M
authors.initials: RM
authors.lastname: Belizaire
authors.forename: Priya S
authors.initials: PS
authors.lastname: Prakash
authors.forename: Jillian R
authors.initials: JR
authors.lastname: Richter
authors.forename: Bryce R
authors.initials: BR
authors.lastname: Robinson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: Charles C
authors.initials: CC
authors.lastname: Caldwell
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lentsch
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Pritts
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001793:Blood Preservation / Q000009:adverse effects*; D055252:Cell-Derived Microparticles; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D004912:Erythrocytes / Q000166:cytology; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism*; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000150:complications / Q000276:immunology / Q000628:therapy*
chemical_list: D015415:Biomarkers