title: Human platelets target dendritic cell differentiation and production of proinflammatory cytokines.
abstract: BACKGROUND
  Dendritic cells (DCs) are the most potent antigen-presenting cells that initiate and regulate immune responses. They are unique in their feature to produce bioactive interleukin (IL)-12, a major proinflammatory cytokine connecting innate and adaptive immunity. Platelets (PLTs) are highly reactive components of the circulatory system with fundamental importance in hemostasis and innate immunity. Recently, immunomodulatory capacities of single specific human PLT-derived products on DC effector functions were identified. To improve the understanding of PLT-DC interactions, this study investigates the influence of intact resting and activated PLTs on DC phenotype and key functions.
  
  
  METHODS
  Magnetic beads sorted CD14+ cells were expanded in the presence and absence of resting or activated PLTs. DC differentiation, maturation, allostimulatority capacity, antigen uptake, and cytokine profile were estimated to control group.
  
  
  RESULTS
  Activated PLTs potently impaired DC differentiation according to CD1a expression (mean reduction, 62%; p < 0.05). Production of IL-12p70 and tumor necrosis factor-alpha was reduced in the presence of resting (mean reduction, 46 and 55%, respectively; p < 0.05) as well as activated PLTs (mean reduction, 63 and 49%, respectively; p < 0.05). In contrast to the suppression of proinflammatory cytokines, activated PLTs increased production of the immunoregulatory cytokine IL-10 by DCs (mean increase, 52%; p < 0.05). DC allostimulatority capacity, antigen uptake, and phenotypic maturation remained unaffected.
  
  
  CONCLUSIONS
  It is proposed that intact PLTs connect immunity and hemostasis by interfering with DC differentiation and cytokine production. This interference might be of importance in clinical settings, such as DC therapy and PLT transfusions.
authors: Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Giessen, Germany. Karin.Kissel@immunologie.med.uni-giessen.de
authors: Karin
authors: K
authors: Kissel
authors: Seda
authors: S
authors: Berber
authors: Angelika
authors: A
authors: Nockher
authors: Sentot
authors: S
authors: Santoso
authors: Gregor
authors: G
authors: Bein
authors: Holger
authors: H
authors: Hackstein