Human platelets target dendritic cell differentiation and production of proinflammatory cytokines

• Published in: Transfusion (Philadelphia, Pa.) Vol. 46; no. 5; pp. 818 - 827
• Main Authors: Kissel, Karin, Berber, Seda, Nockher, Angelika, Santoso, Sentot, Bein, Gregor, Hackstein, Holger
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.05.2006; Blackwell Publishing
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood coagulation. Blood cells; Blood Platelets - cytology; Blood Platelets - immunology; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Communication - immunology; Cell Differentiation - immunology; Cells, Cultured; Coculture Techniques; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - transplantation; Fundamental and applied biological sciences. Psychology; Humans; Immunity, Innate; Inflammation - immunology; Interleukin-12 - immunology; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Medical sciences; Molecular and cellular biology; Platelet; Platelet Activation - immunology; Platelet Transfusion; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Human; Platelet; Transfusion; Cell differentiation; Cytokine
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/j.1537-2995.2006.00802.x

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. STUDY DESIGN AND 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‐α 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. CONCLUSION:  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.