Characterization of lead-recycling facility emissions at various workplaces: Major insights for sanitary risks assessment

Most available studies on lead smelter emissions deal with the environmental impact of outdoor particles, but only a few focus on air quality at workplaces. The objective of this study is to physically and chemically characterize the Pb-rich particles emitted at different workplaces in a lead recycling plant. A multiscale characterization was conducted from bulk analysis to the level of individual particles, to assess the particles properties in relation with Pb speciation and availability. Process PM from various origins were sampled and then compared; namely Furnace and Refining PM respectively present in the smelter and at refinery workplaces, Emissions PM present in channeled emissions. These particles first differed by their morphology and size distribution, with finer particles found in emissions. Differences observed in chemical composition could be explained by the industrial processes. All PM contained the same major phases (Pb, PbS, PbO, PbSO4 and PbO·PbSO4) but differed on the nature and amount of minor phases. Due to high content in PM, Pb concentrations in the CaCl2 extractant reached relatively high values (40mgL−1). However, the ratios (soluble/total) of CaCl2 exchangeable Pb were relatively low (<0.02%) in comparison with Cd (up to 18%). These results highlight the interest to assess the soluble fractions of all metals (minor and major) and discuss both total metal concentrations and ratios for risk evaluations. In most cases metal extractability increased with decreasing size of particles, in particular, lead exchangeability was highest for channeled emissions. Such type of study could help in the choice of targeted sanitary protection procedures and for further toxicological investigations. In the present context, particular attention is given to Emissions and Furnace PM. Moreover, exposure to other metals than Pb should be considered

A field study of lead phytoextraction by various scented Pelargonium cultivars

Phytoremediation appears to be a promising technique for metal soil clean up, although its successful application on a large scale still remains a challenge. Field experiments for six scented Pelargonium cultivars, conducted on two Pb-contaminated calcareous and acidic soils, revealed vigorous plant growth, with no symptoms of morpho-phytotoxicity in spite of high Pb accumulation levels. Lead contents in the harvestable parts of all plants grown on the acidic and more contaminated soil were significantly higher than those grown on the calcareous soil. Three cultivars (Attar of Roses, Clorinda and Atomic Snowflake) are Pb-hyperaccumulator plants: they accumulated more than 1000 mg Pb kg1 DW, with high biomass produced

Secretion and lysophospholipase D activity of autotaxin by adipocytes are controlled by N-glycosylation and signal peptidase.: Secretion and Activity of Adipocyte Autotaxin

Autotaxin (ATX) is a lysophospholipase D involved in synthesis of lysophosphatidic acid (LPA). ATX is secreted by adipocytes and is associated with adipogenesis and obesity-associated diabetes. Here we have studied the mechanisms involved in biosynthesis and secretion of ATX by mouse 3T3-F442A adipocytes. We found that inhibition of N-glycosylation with tunicamycin or by double point deletion of the amino-acids N53 and N410 of ATX inhibit its secretion. In addition, N-glycosidase treatment and point deletion of the amino-acid N410 inhibits the lysophospholipase D activity of ATX. Analysis of the amino-acid sequence of mouse ATX shows the presence of a N-terminal signal peptide. Treatment with the signal peptidase inhibitor globomycin inhibits ATX secretion by adipocytes. Transfection in Cos-7 cells of site-directed deleted ATX shows that ATX secretion is dependent on the hydrophobic core sequence of the signal peptide, not on the putative signal peptidase cleavage site sequence. Analysis of the amino-acid sequence of mouse ATX also reveals the presence of a putative cleavage site by the protein convertase furin. Treatment of adipocytes with the furin inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethylketone does not modified secretion or lysophospholipase D activity of ATX. Transfection in Cos-7 cells of site-directed deleted ATX shows that the furin recognition site is not required for secretion or lysophospholipase D activity of ATX. In conclusion, the present work demonstrates the crucial role of N-glycosylation in secretion and activity of ATX. The present work also confirms the crucial role signal peptidase in secretion of ATX by adipocytes

Lysophosphatidic acid-1-receptor targeting agents for fibrosis.

International audienceINTRODUCTION: The presence of fibrosis is associated with alterations in organ architecture and is responsible for the morbidity of diseases including pneumopathies, systemic sclerosis, liver cirrhosis, chronic cardiovascular diseases, progressive kidney diseases and diabetes. Although a growing number of pro-fibrotic molecules, mediators and other pathways have been reported, there are currently very few antifibrotic molecules being evaluated in clinical trials. AREAS COVERED: Current knowledge about the contribution of lysophosphatidic acid (LPA), a bioactive mediator acting via specific G-protein coupled receptors (LPAR), in the etiology of fibrosis. In a number of organs, fibrosis is associated with increased LPA production as well as with increased expression of some LPAR subtypes (mainly LPA1R). LPAR(-/-) knockout mice and treatment of animal models with specific antagonists clearly demonstrate the contribution of LPA1R subtype to the development of kidney, lung, vascular and dermal fibrosis. The involvement of LPA in liver fibrosis is also strongly suspected but still unproven. EXPERT OPINION: Experiments in animal models clearly demonstrate that LPA1R antagonists have interesting anti-fibrotic potencies. This reveals promising perspectives for the design of new therapeutic approaches to prevent fibrosis-associated diseases. Nevertheless, the number of efficient LPA1R antagonists currently available is still low, and none of them has been used in clinical trials so far

Lysophosphatidic acid and renal fibrosis.

International audienceThe development of fibrosis involves a multitude of events and molecules. Until now the majority of these molecules were found to be proteins or peptides. But recent data show significant involvement of the phospholipid lysophosphatidic acid (LPA) in the development of pulmonary, liver and renal fibrosis. The latest data on the role of LPA and the G-protein-coupled LPA1 receptor in the development of renal fibrosis will be discussed. LPA1-receptor activation was found to be associated with increased vascular leakage and increased fibroblast recruitment in pulmonary fibrosis. Furthermore, in renal fibrosis LPA1-receptor activation stimulates macrophage recruitment and connective tissue growth factor expression. The observations make this receptor an interesting alternative and new therapeutic target in fibrotic diseases

Lysophosphatidic acid inhibits adipocyte differentiation via lysophosphatidic acid 1 receptor-dependent down-regulation of peroxisome proliferator-activated receptor gamma2.

Lysophosphatidic acid (LPA) is a bioactive phospholipid acting via specific G protein-coupled receptors that is synthesized at the extracellular face of adipocytes by a secreted lysophospholipase D (autotaxin). Preadipocytes mainly express the LPA(1) receptor subtype, and LPA increases their proliferation. In monocytes and CV1 cells LPA was recently reported to bind and activate peroxisome proliferator-activated receptor gamma (PPARgamma), a transcription factor also known to play a pivotal role in adipogenesis. Here we show that, unlike the PPARgamma agonist rosiglitazone, LPA was unable to increase transcription of PPARgamma-sensitive genes (PEPCK and ALBP) in the mouse preadipose cell line 3T3F442A. In contrast, treatment with LPA decreased PPARgamma2 expression, impaired the response of PPARgamma-sensitive genes to rosiglitazone, reduced triglyceride accumulation, and reduced the expression of adipocyte mRNA markers. The anti-adipogenic activity of LPA was also observed in the human SGBS (Simpson-Golabi-Behmel syndrome) preadipocyte cell line, as well as in primary preadipocytes isolated from wild type mice. Conversely, the anti-adipogenic activity of LPA was not observed in primary preadipocytes from LPA(1) receptor knock-out mice, which, in parallel, exhibited a higher adiposity than wild type mice. In conclusion, LPA does not behave as a potent PPARgamma agonist in adipocytes but, conversely, inhibits PPARgamma expression and adipogenesis via LPA(1) receptor activation. The local production of LPA may exert a tonic inhibitory effect on the development of adipose tissue

LPA1 receptor activation promotes renal interstitial fibrosis.

International audienceTubulointerstitial fibrosis in chronic renal disease is strongly associated with progressive loss of renal function. We studied the potential involvement of lysophosphatidic acid (LPA), a growth factor-like phospholipid, and its receptors LPA(1-4) in the development of tubulointerstitial fibrosis (TIF). Renal fibrosis was induced in mice by unilateral ureteral obstruction (UUO) for up to 8 d, and kidney explants were prepared from the distal poles to measure LPA release into conditioned media. After obstruction, the extracellular release of LPA increased approximately 3-fold. Real-time reverse transcription PCR (RT-PCR) analysis demonstrated significant upregulation in the expression of the LPA(1) receptor subtype, downregulation of LPA3, and no change of LPA2 or LPA4. TIF was significantly attenuated in LPA1 (-/-) mice compared to wild-type littermates, as measured by expression of collagen III, alpha-smooth muscle actin (alpha-SMA), and F4/80. Furthermore, treatment of wild-type mice with the LPA1 antagonist Ki16425 similarly reduced fibrosis and significantly attenuated renal expression of the profibrotic cytokines connective tissue growth factor (CTGF) and transforming growth factor beta (TGFbeta). In vitro, LPA induced a rapid, dose-dependent increase in CTGF expression that was inhibited by Ki16425. In conclusion, LPA, likely acting through LPA1, is involved in obstruction-induced TIF. Therefore, the LPA1 receptor might be a pharmaceutical target to treat renal fibrosis