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

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.</p> <p><b>What is the context?</b></p> <p></p><p>Premature neonates in the neonatal intensive care unit (NICU) often receive platelet transfusions to prevent bleeding, but use of higher transfusion thresholds has been linked to increased death, bleeding, lung disease, and developmental delays.</p><p>This may be due to a “mismatch” between the neonate’s platelets and the transfused platelets from adult donors.

Compared to neonatal platelets, adult platelets are more active and potentially more inflammatory.</p><p>Platelets help regulate inflammation through interactions with immune cells like monocytes, but how exposure to neonatal vs. adult platelets affects the monocyte inflammatory response is unknown.</p><p></p> <p>Premature neonates in the neonatal intensive care unit (NICU) often receive platelet transfusions to prevent bleeding, but use of higher transfusion thresholds has been linked to increased death, bleeding, lung disease, and developmental delays.</p> <p>This may be due to a “mismatch” between the neonate’s platelets and the transfused platelets from adult donors.

Compared to neonatal platelets, adult platelets are more active and potentially more inflammatory.</p> <p>Platelets help regulate inflammation through interactions with immune cells like monocytes, but how exposure to neonatal vs. adult platelets affects the monocyte inflammatory response is unknown.</p> <p><b>What is new?</b></p> <p></p><p>In this study, we found that monocytes isolated from neonates responded differently after exposure to adult vs. neonatal platelets.</p><p>Exposure to adult platelets increased CCR2 and CCR5 on monocytes, priming them to migrate from blood into tissue – an effect driven by platelet P-selectin binding to the monocyte receptor PSGL-1.</p><p></p> <p>In this study, we found that monocytes isolated from neonates responded differently after exposure to adult vs. neonatal platelets.</p> <p>Exposure to adult platelets increased CCR2 and CCR5 on monocytes, priming them to migrate from blood into tissue – an effect driven by platelet P-selectin binding to the monocyte receptor PSGL-1.</p> <p><b>What is the Impact?</b></p> <p></p><p>These findings show the need to better understand how platelet immune function changes with development, so transfusion products can be better matched to a patient’s age – reducing harmful inflammation and improving outcomes.</p><p></p> <p>These findings show the need to better understand how platelet immune function changes with development, so transfusion products can be better matched to a patient’s age – reducing harmful inflammation and improving outcomes.</p>