Platelets induce Pai-1 mRNA expression in monocytes through TGF-BETA

Introduction: Plasminogen activator inhibitor type-1 (PAI-1) is a physiological modulator of fibrinolysis. High plasma PAI-1 is associated with the 4G/5G promoter polymorphism and with increased cardiovascular risk. Here we explored the role of platelets in regulating expression of the PAI-1 gene in monocytes. Methods: Blood from PAI-1 4G/5G genotyped volunteers (n=6) was incubated with the platelet GPVI-specific agonist, cross-linked collagen related peptide (CRP-XL), in the presence or absence of Mab 9E1 that blocks the binding of P-selectin to PSGL1. Monocytes were isolated by +ve selection on CD14 beads and monocyte PAI-1 mRNA expression was measured by real-time PCR. Results: Activation of platelets with CRP-XL resulted in platelets binding to >70% of monocytes and was accompanied by >5000-fold induction of PAI-1 mRNA, peaking at 4hrs. PAI-1 expression was independent of the 4G/5G genotype. Blocking the binding of platelets to monocytes enhanced PAI-1 induction (p<0.05 at 4 hrs). Incubation of isolated monocytes with the releasate from CRP-XL stimulated platelets also led to PAI-1 mRNA expression. The platelet secretome contains >100 different proteins. To identify the soluble factor(s) responsible for induction of PAI-1, neutralizing antibodies to likely candidates were added to monocytes incubated with the platelet releasate. Anti- TGF-beta inhibited platelet releasate-mediated PAI-1 mRNA induction by >80%. Monocyte PAI-1 was also induced by stimulation of PSGL-1 with a P-selectin-Fc chimera, in the absence of platelets, which was also blocked by the TGF-beta antibody. Conclusions: These results suggest that platelets induce PAI-1 mRNA in monocytes predominantly via TGF-beta, released from both platelets, and monocytes via activation by PSGL-1 signalling.This stimulation is independent of 4G/5G genotype

Energy efficiency and greenhouse gas emissions of different supply chains: a comparison of French, UK and Belgian cases

Freight transportation system is critical to economic activity but it carries significant environmental costs, notably GHG emissions and climate change : energy use and corresponding CO2 emissions is increasing faster in freight transport than in other sectors and this increase is primarily the result of increased trade. This paper compares the transport activities, associated energy consumption and CO2 emissions of different supply chains for a range of products in three countries: Belgium, France and United Kingdom. Among the products considered are furniture and ‘fruits & vegetables’. For each of these products, different supply chains, involving more or less transport activity and associated energy consumption are analysed in each country. The comparison highlights some of the main factors that influence GHG emissions for different supply chains and illustrates how they vary according to product and country of final distribution. In more detail, the paper addresses the main differences between the supply chains of these products namely, the origin of their sourcing, the logistical organisation between production and retail and different types of retail outlet. The origin of the sourcing impact is mainly related to distance. The impact of the logistical organisation between raw material and retail on GHG emissions is linked to the mode and vehicle choice and to the load factor. As for retail, the consumer trip emissions, between his home and the retail outlet, are also an important part of the whole supply chain emissions. It is worthwhile to notice that our goal in this project is to consider the whole supply chain, from production to consumption. Therefore a particular focus is put on the mobility behaviours of consumers purchasing the studied products during their shopping and dropping back home activities related to these products. Especially a web based survey has been conducted and the gathered results offer an opportunity for drawing a more detailed picture of the associated CO2 emissions. This paper uses the results of an ongoing research on supply chain energy efficiency, funded by ADEME (the French Energy Agency) through the French program on transport research (PREDIT). This research is based on a comprehensive review of the various approaches to quantifying the environmental impacts of supply chains together with data collection from a range of organisations including manufacturers, retailers and transport companies. We will first present the developed methodologies, then the results corresponding to each studied product will be described. A discussion of the potential application of the research approach to the wider debate about the environmental impact of freight transport and the scope for GHG emissions reduction targets to be achieved will be included.

Energy efficiency and greenhouse gas emissions of different supply chains: a comparison of French, UK and Belgian cases

Freight transportation system is critical to economic activity but it carries significant environmental costs, notably GHG emissions and climate change : energy use and corresponding CO2 emissions is increasing faster in freight transport than in other sectors and this increase is primarily the result of increased trade. This paper compares the transport activities, associated energy consumption and CO2 emissions of different supply chains for a range of products in three countries: Belgium, France and United Kingdom. Among the products considered are furniture and fruits & vegetables. For each of these products, different supply chains, involving more or less transport activity and associated energy consumption are analysed in each country. The comparison highlights some of the main factors that influence GHG emissions for different supply chains and illustrates how they vary according to product and country of final distribution. In more detail, the paper addresses the main differences between the supply chains of these products namely, the origin of their sourcing, the logistical organisation between production and retail and different types of retail outlet. The origin of the sourcing impact is mainly related to distance. The impact of the logistical organisation between raw material and retail on GHG emissions is linked to the mode and vehicle choice and to the load factor. As for retail, the consumer trip emissions, between his home and the retail outlet, are also an important part of the whole supply chain emissions. It is worthwhile to notice that our goal in this project is to consider the whole supply chain, from production to consumption. Therefore a particular focus is put on the mobility behaviours of consumers purchasing the studied products during their shopping and dropping back home activities related to these products. Especially a web based survey has been conducted and the gathered results offer an opportunity for drawing a more detailed picture of the associated CO2 emissions. This paper uses the results of an ongoing research on supply chain energy efficiency, funded by ADEME (the French Energy Agency) through the French program on transport research (PREDIT). This research is based on a comprehensive review of the various approaches to quantifying the environmental impacts of supply chains together with data collection from a range of organisations including manufacturers, retailers and transport companies. We will first present the developed methodologies, then the results corresponding to each studied product will be described. A discussion of the potential application of the research approach to the wider debate about the environmental impact of freight transport and the scope for GHG emissions reduction targets to be achieved will be included.