title: Treatment of platelets with riboflavin and ultraviolet light mediates complement activation and suppresses monocyte interleukin-12 production in whole blood.
abstract: OBJECTIVE
  Pathogen inactivation (PI) and storage may alter the immunomodulatory capacity of platelets (PLTs). The aim of this study was to examine the effect of PI (Riboflavin and ultraviolet light treatment) and storage on the capacity of PLTs to induce cytokine responses in recipient inflammatory cells.
  
  
  METHODS
  A pool and split design was used to prepare untreated and PI-treated buffy coat-derived platelet concentrates (PCs). Samples were taken on days 2 and 7 postcollection and incubated with ABO/RhD-matched fresh whole blood for 6 h with or without lipopolysaccharide (LPS). The intracellular production of IP-10, MCP-1, MIP-1α, IL-8, IL-6, IL-10, IL-12, TNF-α and MIP-1β in monocytes and neutrophils was assessed using flow cytometry. Complement proteins in PLT supernatants were measured using a cytometric bead array.
  
  
  RESULTS
  PLTs and PLT supernatant (both untreated and PI-treated) resulted in modulation of intracellular MIP-1β and IL-12 production in monocytes. Compared to untreated PLTs, PI-treated PLTs resulted in significantly lower LPS-induced monocyte IL-12 production (day 7). The concentration of C3a and C5a (and their desArg forms) was significantly increased in PLT supernatants following PI.
  
  
  CONCLUSIONS
  PI results in decreased LPS-induced monocyte IL-12 production and increased complement activation. The association between platelet-induced complement activation and IL-12 production warrants further investigation.
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Sydney, NSW, Australia.
authors.forename: Y S
authors.initials: YS
authors.lastname: Loh
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Brisbane, QLD, Australia.
authors.forename: M M
authors.initials: MM
authors.lastname: Dean
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Sydney, NSW, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Johnson
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Sydney, NSW, Australia.
authors.forename: D C
authors.initials: DC
authors.lastname: Marks
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D001793:Blood Preservation / Q000379:methods; D003167:Complement Activation / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D018664:Interleukin-12 / Q000097:blood*; D009000:Monocytes / Q000378:metabolism*; D012256:Riboflavin / Q000009:adverse effects / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D018664:Interleukin-12; D012256:Riboflavin
keywords: C3a; C5a; IL-12; PLT immunomodulation; pathogen inactivation