THP-1 l

Platelet-Derived Microvesicles Modulate Cytokine and Lipid Mediator Profiles in THP-1 Monocytes

Monocytes are circulating immune cells that migrate to inflamed tissues and differentiate into macrophages, where they play a dual role in regulating pro-inflammatory and pro-resolving responses through cytokine and lipid mediator secretion. Platelet-derived microvesicles (PMVs), released during platelet activation, infiltrate inflamed areas and interact with monocytes and macrophages, facilitating the transfer of bioactive contents. While these interactions have been observed, their functional consequences on monocyte/macrophage inflammatory profiles remain poorly understood.

In this study, PMVs are shown to be internalized by human THP-1 monocytes. The interaction with THP-1 cells occurs rapidly, with 60 % of cells interacting with PMVs within one hour. When cells are differentiated to M0 and M1 macrophages, interactions with PMVs only peak after 24 h. Interaction of cells with PMVs resulted in an increased capacity to synthesize cyclooxygenase- and lipoxygenase-derived lipid mediators of inflammation, especially in M1 cells. Cytokine production was also influenced in a cell-state-dependent manner. PMVs had no impact on undifferentiated THP-1 cells but enhanced the production of several cytokines in M0 cells as well as IL-23 and IL-6 in M1 macrophages. When stimulated with lipopolysaccharides, PMV-treated M0 macrophages demonstrated elevated production of the anti-inflammatory cytokine IL-10, while M1 macrophages exhibited increased secretion of IL-1β, MCP-1, and IL-6, highlighting an effect on pro-inflammatory cytokine production. These findings reveal that PMVs selectively modulate the inflammatory cytokine and lipid mediator profiles of monocytes and macrophages depending on their differentiation state.