Open AccessPlatelets regulate leucocyte responses to Toll‐like receptor stimulation
Author(s) -
Hally Kathryn E,
La Flamme Anne C,
Harding Scott A,
Larsen Peter D
Publication year - 2018
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1002/cti2.1036
Subject(s) - tlr2 , chemokine , platelet , peripheral blood mononuclear cell , immunology , cytokine , platelet activation , monocyte , tumor necrosis factor alpha , tlr4 , granulocyte , medicine , endocrinology , biology , inflammation , in vitro , biochemistry
Objectives Platelets are important regulators of vascular thrombosis and inflammation and are known to express Toll‐like receptors ( TLR s). Through TLR s, platelets mediate a number of responses by interacting with leucocytes. Here, we report the extent to which platelets modulate in vitro peripheral blood mononuclear cells ( PBMC s) and granulocyte responses to TLR 4, TLR 2/1 and TLR 2/6 stimulation in healthy subjects. Methods Peripheral blood mononuclear cells and granulocytes from 10 healthy volunteers were cultured alone or cocultured with platelets. Cultures were left unstimulated or stimulated with 1 or 100 ng mL −1 of either LPS ( TLR 4 agonist), Pam3 CSK 4 ( TLR 2/1 agonist) or fibroblast‐stimulating lipopeptide ( FSL )‐1 ( TLR 2/6 agonist). Neutrophil activation ( CD 66b expression), monocyte activation ( HLA ‐ DR ), granulocyte elastase production and PBMC cytokine and chemokine production were examined. Results Platelet coculture decreased neutrophil CD 66b expression in response to LPS , Pam3 CSK 4 and FSL ‐1, and modestly decreased monocyte HLA ‐ DR expression in response to low‐dose LPS . Platelets reduced granulocyte elastase secretion in response to low doses of all TLR agonists tested. In response to LPS , platelet coculture reduced IL ‐6, tumor necrosis factor ( TNF )‐α and MIP ‐1β production, and increased IL ‐10 production by PBMC s. In response to FSL ‐1, platelets increased IL ‐6, IL ‐10 and MIP ‐1β production, but reduced TNF ‐α production. Platelet coculture did not alter PBMC cytokine/chemokine production in response to Pam3 CSK 4. Conclusion This study challenges the notion that platelets act solely in a pro‐inflammatory manner. Rather, platelets are complex immunomodulators that regulate leucocyte responses to TLR stimulation in a TLR agonist‐specific manner. Platelets may modulate leucocyte responses to dampen inflammation, and this platelet effect may play an important role in reducing inflammation‐mediated host damage.