Platelet–leukocyte interactions. (Phase I) Neutrophils (N) interact with circulating platelets (PLT): after recognition of platelet P-selectin by the P-selectin granulocyte ligand 1 (PSGL1), neutrophils implement their engagement with platelets by upregulating Mac-1 (also known as αMβ2 or CD11b/CD18), a surface integrin that interacts with platelet-bound fibrinogen in cooperation with glycoprotein (GP) IIbIIIa (also known as α2bβ3 integrin). The activation of neutrophils (possibly further enhanced by CD40–CD40 ligand (CD40L) interactions) results in the release of enzymatic moieties such as myeloperoxidase (MPO), proteinase 3 (PR3) and of the prestored soluble pattern recognition receptor pentraxin (PTX)3 as well as in the expression of tissue factor (TF), which in turn promotes thrombin generation. Platelets also release various bioactive signals such as leukotrienes (LTs), high mobility group box 1 protein (HMGB1), platelet-derived growth factor (PDGF), transforming growth factor beta (TGFβ), lysosphingolipids (LPs), and 5-hydroxytryptamine (5HT). (Phase II) Recognition of phosphatidylserine (P-Ser) on platelets prompts their phagocytic clearance and quenches their procoagulant capacity; neutrophil ADPases break the auto/paracrine loop of ADP-mediated platelet activation. Neutrophils that had phagocytosed platelets become largely anergic after degranulation.