Objective-CD40 ligand is a thromboinflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40 ligand (sCD40L), which has been shown to influence platelet activation, although its exact functional impact on platelets and the underlying mechanisms remain undefined. We aimed to determine the impact and the signaling mechanisms of sCD40L on platelets. Methods and Results-sCD40L strongly enhances platelet activation and aggregation. Human platelets treated with a mutated form of sCD40L that does not bind CD40, and CD40 Ϫ/Ϫ mouse platelets failed to elicit such responses. Furthermore, sCD40L stimulation induces the association of the tumor necrosis factor receptor-associated factor-2 with platelet CD40. Notably, sCD40L primes platelets through activation of the small GTPase Rac1 and its downstream target p38 mitogen-activated protein kinase, which leads to platelet shape change and actin polymerization. Moreover, sCD40L exacerbates thrombus formation and leukocyte infiltration in wild-type mice but not in CD40 Ϫ/Ϫ mice. Conclusion-sCD40L enhances agonist-induced platelet activation and aggregation through a CD40-dependent tumor necrosis factor receptor-associated factor-2/Rac1/p38 mitogen-activated protein kinase signaling pathway. Thus, sCD40L is an important platelet primer predisposing platelets to enhanced thrombus formation in response to vascular injury. This may explain the link between circulating levels of sCD40L and cardiovascular diseases. M ultiple lines of evidence now support a plethora of inflammatory mediators potentially involved in the pathogenesis of vascular disease. Among these, the CD40 ligand (CD40L)/CD40 dyad has been the focus of much attention, and circulating levels of soluble CD40L (sCD40L) are now considered reliable predictors of cardiovascular events. [1][2][3][4] CD40L is a 48-kDa trimeric transmembrane protein belonging to the tumor necrosis factor superfamily originally identified on cells of the immune system. 5,6 Interaction of CD40L with its respective receptor on B cells, CD40, a 39-kDa glycoprotein from the tumor necrosis factor receptor family, is of critical importance for immunoglobulin isotype switching during the immune response. 7 Today, we know that these 2 molecules are also present on cells of the vascular system, including endothelial cells, monocytes/macrophages, smooth muscle cells, and platelets, 8,9 and have important implications in inflammatory reactions, through upregulation of cell adhesion molecules and production of proinflammatory cytokines, chemokines, growth factors, matrix metalloproteinases, and procoagulants. 8,10 -12 The involvement of the CD40L/CD40 dyad in thromboinflammation has been highlighted in all pathogenic phases of atherosclerosis, including endothelial dysfunction, platelet activation, thrombosis, and neointima formation. [13][14][15][16][17][18][19][20] Platelets are highly specialized blood cells of paramount importance in normal hemostasis and thromboinflammatory complications. The pio...

The fully energy-damped yields from the 35 Clϩ 12 C reaction have been systematically investigated using particle-particle coincidence techniques at a 35 Cl bombarding energy of ϳ8 MeV/nucleon. The fragmentfragment correlation data show that the majority of events arises from a binary-decay process with rather large numbers of secondary light-charged particles emitted from the two excited exit fragments. No evidence is observed for ternary break-up events. The binary-process results of the present measurement, along with those of earlier, inclusive experimental data obtained at several lower bombarding energies are compared with predictions of two different kinds of statistical model calculations. These calculations are performed using the transition-state formalism and the extended Hauser-Feshbach method and are based on the available phase space at the saddle point and scission point of the compound nucleus, respectively. The methods give comparable predictions and are both in good agreement with the experimental results thus confirming the fusionfission origin of the fully damped yields. The similarity of the predictions for the two models supports the claim that the scission point configuration is very close to that of the saddle point for the light 47 V compound system. The results also give further support for the specific mass-asymmetry-dependent fission barriers needed in the transition-state calculation. ͓S0556-2813͑96͒02407-7͔