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INVESTIGADORES

ERRASTI Andrea Emilse

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Título:

Platelets Promote Monocyte Polarization to a M1 Phenotype upon LPS Stimulation.

Autor/es:

M. SCHATTNER; A. CARESTIA; H.A. MENA; A.E. ERRASTI; S. NEGROTTO; E.A. CARRERA SILVA

Lugar:

Berlin

Reunión:

Congreso; ISTH Congress 2017; 2017

Institución organizadora:

International Society on Thrombosis and Haemostasis

Resumen:

Background: Platelets and monocyte/macrophages interaction appears to play a relevant role in the pathophysiology of sepsis. However, it has been reported that platelets can positively or negatively regulate monocytes/macrophages responses. Although the reasons for these discrepancies are not clear, we hypothesize that LPS concentrations and stimulation times are critical determinants. Aims: To clarify the role of platelets in the biology of monocytes/ macrophages upon LPS challenge, we analyzed the monocyte inflammatory response at day 1 and 2 and their polarization at day 5 in the presence of platelets and broad range of LPS concentrations. Methods: Human monocytes were purified by positive selection, incubated with autologous platelets and stimulated with LPS. Results: LPS induced the release of pro (TNFα/IL-6)- and anti (IL-10/ IL-4)-inflammatory cytokines (ELISA) in a LPS concentration-dependent manner after 1 and 2 days, respectively. Platelets decreased the release of all cytokines at all LPS concentrations (Fig.1). While low LPS concentrations differentiated monocytes into M2 macrophages by decreasing CD64 and augmenting CD206 and CD163 (flow cytometry), a more pro-inflammatory phenotype was observed with increasing LPS concentrations (Fig.2). Platelets polarized monocytes predominantly towards M1 phenotype at all LPS concentrations. Accordingly,macrophages derived from platelet/monocyte co-cultures had an increase capacityto produce TNFα and exerted a higher bacterial phagocytic activity (flow cytometry) (Fig.2). Moreover, endothelial cells presented a reduced capability of healing when incubated with supernatants from platelet/monocyte co-culture-derived macrophages (scratch assay) (Fig.2). The skewing effect of platelets on monocyte polarization was abrogated in a transwell assay. Conclusions:Our results demonstrated that, upon LPS stimulation, platelets decrease therelease of both pro and anti-inflammatory cytokines from monocytes but polarize them to M1 phenotype in a cell contact dependent manner.

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