Figure 1.

Known interactions between platelets and neutrophils. These can be mediated by direct contact between platelet and neutrophil receptors or indirectly via secreted ligands or molecules present in plasma. Most of these interactions require either the platelet and/or the neutrophil to be activated. Neutrophils can interact via PSGL-1 or CD40 with P-selectin and CD40L, respectively, on activated platelets. PSGL-1 binding to P-selectin triggers downstream signalling in neutrophils (black solid lines) leading to Mac-1 integrin conformational change from a closed to open conformation (dotted black line). These events can be enhanced by cooperative signals from CXCL1/4/7 immobilised by proteoglycans binding to CXCR2 or Mac-1. Activated Mac-1 can further promote binding to platelets directly via GPIbα or ICAM-2 or indirectly via fibrinogen-bound α_IIbβ₃. Additional depicted interactions are granule-release HMGB1 from platelets with neutrophil RAGE receptor promoting further neutrophil activation and LL-37 released from neutrophils (dotted red line) activating platelets via GPVI. Lastly, direct binding of activated α_IIbβ₃ to neutrophil receptor SLC44A2 can trigger neutrophil activation and NET formation. GPIbα- glycoprotein Ibα; GPVI- glycoprotein VI; ICAM-2- intracellular adhesion molecule 2; CD40L- CD40 Ligand; P-sel- P-selectin (CD62P); CXCL- C-X-C Motif Chemokine Ligand; HMGB1- High mobility group box 1 protein; PSGL-1- P-selectin glycoprotein ligand; SLC44A2- solute carrier family 44 member 2 or CTL-2; MAC-1- macrophage 1 antigen or CD11bCD18 or α_Mβ₂; LL-37—human cathelicidin antimicrobial peptide; RAGE- receptor of advanced glycation end products. Created by Biorender.com.