Journal article
Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion
Journal of Interferon and Cytokine Research, Vol.35(10), pp.821-830
2015
Abstract
The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1β and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1β, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1β significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.
Details
- Title
- Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion
- Authors
- A J Perros (Author) - Queensland University of TechnologyA M Christensen (Author) - Queensland University of TechnologyR L Flower (Author) - Queensland University of TechnologyMelinda M Dean (Author) - Queensland University of Technology
- Publication details
- Journal of Interferon and Cytokine Research, Vol.35(10), pp.821-830
- Publisher
- Mary Ann Liebert Inc. Publishers
- Date published
- 2015
- DOI
- 10.1089/jir.2015.0029
- ISSN
- 1079-9907; 1557-7465; 1079-9907
- Organisation Unit
- School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99513783002621
- Output Type
- Journal article
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- Domestic collaboration
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Immunology
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