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Journal of Inflammation
Published in: Journal of Inflammation 1/2010

Open Access 01-12-2010 | Research

Macrophage pro-inflammatory cytokine secretion is enhanced following interaction with autologous platelets

Authors: Christopher M Scull, William D Hays, Thomas H Fischer

Published in: Journal of Inflammation | Issue 1/2010

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Abstract

Background

Macrophages are the dominant phagocyte at sites of wound healing and inflammation, and the cellular and acellular debris encountered by macrophages can have profound effects on their inflammatory profile. Following interaction with apoptotic cells, macrophages are known to switch to an anti-inflammatory phenotype. Activated platelets, however, are also a major component of inflammatory lesions and have been proposed to be pro-inflammatory mediators. In the present study, we tested the hypothesis that macrophage interaction with activated platelets results in an inflammatory response that differs from the response following phagocytosis of apoptotic cells.

Methods

Human monocyte-derived macrophages (hMDMs) were co-incubated with autologous activated platelets (AAPs) and the platelet-macrophage interaction was examined by electron microscopy and flow cytometry. The cytokines TNF-α, IL-6, and IL-23 were also measured during LPS-activated hMDM co-incubation with AAPs, which was compared to co-incubation with apoptotic lymphocytes. Cytokine secretion was also compared to platelets pre-treated with the gluococorticoid dexamethasone.

Results

Macrophages trapped and phagocytized AAPs utilizing a mechanism that was significantly inhibited by the scavenger receptor ligand fucoidan. LPS-induced macrophage secretion of TNF-α, IL-6, and IL-23 was inhibited by co-incubation with apoptotic cells, but enhanced by co-incubation with AAPs. The platelet-dependent enhancement of LPS-induced cytokines could be reversed by pre-loading the platelets with the glucocorticoid dexamethasone.

Conclusions

The interaction of human macrophages with autologous platelets results in scavenger-receptor-mediated platelet uptake and enhancement of LPS-induced cytokines. Therefore, the presence of activated platelets at sites of inflammation may exacerbate pro-inflammatory macrophage activation. The possibility of reversing macrophage activation with dexamethasone-loaded platelets is a promising therapeutic approach to treating unresolved inflammation.
Appendix
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Metadata
Title
Macrophage pro-inflammatory cytokine secretion is enhanced following interaction with autologous platelets
Authors
Christopher M Scull
William D Hays
Thomas H Fischer
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2010
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/1476-9255-7-53

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