In ALI, inflammation from lipopolysaccharide (LPS) or other pathogens induces generation of unknown platelet GPVI activators. Although fibrin is a strong potential agonist, histones, collagen, or other agonists could be generated to activate GPVI. GPVI activation induces platelet-dependent neutrophil (PMN) recruitment and firm adhesion to the endothelium. This allows for neutrophils to migrate into the alveolar space. In addition, platelet-dependent neutrophil activation can lead to neutrophil extracellular trap formation (NETosis). Overall, the formation of platelet-neutrophil complexes (PNCs) leads to increased edema, brochoalevolar lavage (BAL) proteins, and cytokine generation. Inhibition of GPVI through either genetic deletion or anti-GPVI antibodies decreases neutrophil recruitment and activation, leading to reduced lung damage and hypoxia. Figure prepared with assistance from Diana Lim.