Platelets are a previously unrecognized source of immune-modulatory CXCL14

A. Witte, J. Lu, M. Gawaz (1Tübingen, Germany)

Date: 18.02.2017,
Time: 10:00 - 11:15

Objective: Platelets are the source of a variety of chemokines which are crucial for immune responses due to their immune-modulatory or antimicrobial activity. The relatively newly discovered antimicrobial chemokine CXCL14 is widely expressed in different kinds of tissue and immune cells. The objective of this study was to investigate whether platelets contain CXCL14 and, like other platelet-derived chemokines, whether CXCL14 is released upon activation. Furthermore a possible immune-modulatory function of platelet derived CXCL14 was investigated.

Methods: Flow cytometry, western blot analysis, Boyden Chamber migration assays, scratch assay (HUVECs)

Results: Western Blot analyses with isolated platelets show that human as well as murine platelets express the chemokine CXCL14, also known as BRAK, which was unknown until now. Upon activation of human platelets in platelet-rich-plasma (PRP) with different agonists, CXCL14 cell surface expression was significantly enhanced indicating that CXCL14 is released and can bind back to the platelet membrane. Furthermore, activation of platelets with increasing concentrations of Collagen Related Peptide (CRP) correlated with CXCL14 surface expression. Since CXCL14 is known to be chemotactic for monocytes and NK cells, we investigated the chemotactic effect of platelet-derived CXCL14 on isolated human monocytes. Treatment of activated platelet supernatant with a neutralizing antibody against CXCL14 led to a decreased number of migrated monocytes towards the platelet supernatant, indicating that platelet-derived CXCL14 is involved in chemotactic responses as an immune modulatory chemokine. Blocking the chemokine receptor CXCR4 reduced the number of monocytes migrated towards recombinant CXCL14 in contrast to blocking of CXCR7, which indicates an involvement of CXCR4 in the CXCL14 mediated migration of monocytes. In addition, a scratch assay with HUVECs indicates that platelet-derived CXCL14 counteracts the angiogenic effect of VEGF on these endothelial cells, which might be of importance during wound healing and angiogenesis.

Conclusion: We show that platelets are a source of CXCL14 and that CXCL14 is released upon activation. Platelet derived CXCL14 induces monocyte migration and counteracts the angiogenic effect of VEGF on HUVECs.