Developmental differences in platelet P-selectin expression modulate neonatal monocyte inflammatory responses

Abstract

Neonatal and adult platelets are functionally different, with neonatal platelets being comparatively hypo-reactive to multiple platelet agonists. When transfused, neonates receive platelets from adult donors, resulting in a cellular developmental mismatch. Platelets are key regulators of the monocyte inflammatory response, yet how the developmental stage of the platelet affects this response is unknown. In this study, we modeled this developmental mismatch in vitro to investigate the neonatal (cord blood) monocyte inflammatory response and migratory phenotype after exposure to either neonatal (cord blood) or adult platelets. Adult platelets expressed more P-selectin on the surface and released more beta-2-microglobulin (B2M) after activation compared to neonatal platelets. While exposure to platelets of either developmental stage increased the release of IL-8 and MCP-1 from neonatal monocytes to a similar degree, exposure to adult platelets induced significantly greater monocyte CCR2 and CCR5 surface expression, consistent with a pro-migratory monocyte phenotype. Blocking P-selectin/PSGL-1 interactions had no effect on platelet induced monocyte cytokine release but completely abrogated monocyte CCR2 and CCR5 surface upregulation. These findings suggest that the monocyte pro-migratory phenotype is regulated by P-selectin exposure, which is influenced by the platelet developmental stage, while monocyte cytokine release is independent of platelet P-selectin expression or developmental stage.