Cold Spring Harbor Symposia on Quantitative Biology, Volume LXVII.© 2002 Cold Spring Harbor Laboratory Press 0-87969-678-8/02. 197 mote not only hemostasis but also inflammation and cell proliferation. These responses include (1) shape change from smooth discs to spheres with numerous filopodia,(2) release of stored granules’ contents that further promote platelet activation and aggregation (ADP, serotonin, coagulation factor V, vWF, and fibrinogen),(3) release of other granule constituents such as chemokines and growth factors,(4) synthesis and release of the platelet activator thromboxane A2,(5) mobilization of P-selectin and CD40L to their surface (P-selectin is an adhesive receptor for platelets and leukocytes, and CD40L is a TNF-like agonist), and other changes on the platelet surface that promote the assembly of coagulation factor complexes to amplify local thrombin generation, and (6) activation of the key integrin αIIb/β3 (Hamberg et al. 1975; Stenberg et al. 1985; Sims et al. 1989; Brass et al. 1997; Henn et al. 1998; Hughes and Pfaff 1998). The latter binds fibrinogen and vWF to mediate platelet–platelet interaction and hence formation of the aggregates that plug damaged vessels (Colman et al. 1994).

In cultured endothelial cells, thrombin causes release of vWF (Hattori et al. 1989), display of P-selectin on the plasma membrane (Hattori et al. 1989), and production of chemokines—actions thought to trigger binding of platelets and leukocytes to the endothelial surface in vivo (Frenette et al. 1996; Subramaniam et al. 1996). Endothelial cells change shape and endothelial monolayers show increased permeability in response to thrombin (Lum and Malik 1994)—actions predicted to promote local transudation of plasma proteins and edema (Cirino et al. 1996). Thrombin can also regulate blood vessel diameter by endothelial-dependent vasodilation; in the absence of endothelium, thrombin’s actions on smooth muscle cells evoke vasoconstriction. In fibroblast and