Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research

No abstract available

Lactoferrin Inhibits the Lipopolysaccharide-Induced Expression and Proteoglycan-Binding Ability of Interleukin-8 in Human Endothelial Cells

Interleukin-8 (IL-8), a C-X-C chemokine bound to endothelium proteoglycans, initiates the activation and selective recruitment of leukocytes at inflammatory foci. We demonstrate that human lactoferrin, an antimicrobial lipopolysaccharide (LPS)-binding protein, decreases both IL-8 mRNA and protein expression induced by the complex Escherichia coli 055:B5 LPS/sCD14 in human umbilical vein endothelial cells. The use of recombinant lactoferrins mutated in the LPS-binding sites indicates that this inhibitory effect is mediated by an interaction of lactoferrin with LPS and CD14s that suppresses the endotoxin biological activity. Furthermore, since dimeric IL-8 and lactoferrin are both proteoglycan-binding molecules, the competition between these proteins for heparin binding was investigated. Lactoferrin strongly inhibited the interaction of radiolabeled IL-8 to immobilized heparin, whereas a lactoferrin variant lacking the amino acid residues essential for heparin binding was not inhibitory. Moreover, this process is specific, since serum transferrin, a glycoprotein whose structure is close to that of lactoferrin, did not prevent the interaction of IL-8 with heparin. These results suggest that the anti-inflammatory properties of lactoferrin during septicemia are related, at least in part, to the regulation of IL-8 production and also to the ability of lactoferrin to compete with chemokines for their binding to proteoglycans

A visibility map established using a geographic information system (Puy-de-Dôme)

Dans le cadre d'une étude préalable au classement de la Chaîne des Puys, nous avons mis au point une méthode originale permettant de quantifier les contraintes paysagères. La méthode proposée repose sur l'analyse de l'exposition du site aux regards à partir de points de vue privilégiés. Un indice d'exposition aux regards est ainsi défini puis calculé pour tout élément de surface de la zone étudiée à partir de chaque point de vue. Cet indice tient compte de la distance entre le point de vue et l'élément de surface observé, de l'angle selon lequel l'observateur voit cet élément, de la fréquentation du point de vue et de sa nature (point d'arrêt : point sur lequel l'observateur stationne, ou point de passage : point sur lequel l'observateur passe rapidement). La synthèse de ces indices sur la zone étudiée aboutit à un zonage du territoire en cinq classes d'exposition aux regards. L'ensemble des calculs est réalisé sous un système d'information géographique. Le croisement sous système d'information géographique de ce zonage avec les potentialités écologiques et forestières a ensuite permis de définir des zones qui justifient des orientations de gestion forestière spécifiques. L'originalité de cette étude réside dans la mise au point d'un indice objectif d'exposition aux regards, reposant notamment sur l'analyse de la morphologie du relief et de l'angle selon lequel ce relief est vu par l'observateur. Cette analyse met en oeuvre un modèle numérique de terrain, un ensemble de données géographiques décrivant les contraintes écologiques et forestières, gérés par un système d'information géographique

Etude thermique des bains liquides et son effet sur l’état de surface des pièces fabriquées par le procédé de Fabrication Directe par Projection Laser (FDPL)

La fabrication directe par projection laser (FDPL) est un procédé de prototypage rapide et de fabrication des petites séries de pièces complexes, par simple interaction entre un faisceau laser, un substrat, et une poudre projetée. Ce procédé a été largement étudié ces dernières années, à la fois au niveau des propriétés métallurgiques et mécaniques des matériaux obtenus [1], que de la modélisation thermophysique du procédé [2, 3]. L’un des problèmes récurrents du procédé est la mauvaise qualité des états de surface des pièces élaborées [4], qui est directement liée à la taille, la morphologie et l’hydrodynamique des zones fondues. L’objectif de cette étude est de présenter la caractérisation expérimentale des zones fondues générées en FDPL à travers des analyses par caméra rapide, et par différents types d’analyses thermiques (caméra IR, spectrométrie), en considérant un alliage de titane : le Ti-6Al-4V. L’évolution des propriétés des zones fondues avec les paramètres du procédé (distribution spatiale de puissance laser, vitesse de scanning, débit massique) est ensuite discutée dans le détail, et corrélée aux états de surface résultants, afin de proposer des voies d’amélioration du procédé

Effects of human lactoferrin on NK cell cytotoxicity against haematopoietic and epithelial tumour cells

AbstractLactoferrin is an iron-binding glycoprotein implicated in particular in the control of immune functions and cell proliferation. We have investigated its involvement, at inflammatory concentrations, in cancer progression. We report that lactoferrin has a significant effect on natural killer (NK) cell cytotoxicity against haematopoietic and breast epithelial cell lines. Lactoferrin increases cytolysis at a low concentration (10 μg/ml) while at a high concentration (100 μg/ml) it modulates cytolysis depending on the target cell phenotype. By pre-treatment of either NK cells or target cells with lactoferrin, we have demonstrated that the lactoferrin effect is due both to a modulation of NK cell cytotoxicity and the target cell sensitivity to lysis. Lactoferrin binds to 91% of the naturally heterogeneous CD56dim/bright NK cell population and increases the NK cell cytotoxic activity at low concentrations. High concentrations of lactoferrin seem to be toxic for the CD56bright NK cells and decrease NK cell cytotoxicity. Lactoferrin also exerts an effect on target cells depending on the cell phenotype. It does not modify the susceptibility to lysis of haematopoietic cells such as Jurkat and K-562 cells, but does significantly increase that of the breast and colon epithelial cells. We have also demonstrated that lactoferrin inhibits epithelial cell proliferation by blocking the cell cycle progression

Mycobacterial Lipomannan Induces Matrix Metalloproteinase-9 Expression in Human Macrophagic Cells through a Toll-Like Receptor 1 (TLR1)/TLR2- and CD14-Dependent Mechanism

Lipomannans (LM) from various mycobacterial species were found to induce expression and secretion of the matrix metalloproteinase 9 (MMP-9) both in human macrophage-like differentiated THP-1 cells and in primary human macrophages. Inhibition studies using antireceptor-neutralizing antibodies are indicative of a Toll-like receptor 1 (TLR1)/TLR2- and CD14-dependent signaling mechanism. Moreover, LM was shown to down-regulate transcription of the metalloproteinase inhibitor TIMP-1, a major endogenous MMP-9 regulator

Surface nucleolin participates in both the binding and endocytosis of lactoferrin in target cells.

Lactoferrin (Lf), a multifunctional molecule present in mammalian secretions and blood, plays important roles in host defense and cancer. Indeed, Lf has been reported to inhibit the proliferation of cancerous mammary gland epithelial cells and manifest a potent antiviral activity against human immunodeficiency virus and human cytomegalovirus. The Lf-binding sites on the cell surface appear to be proteoglycans and other as yet undefined protein(s). Here, we isolated a Lf-binding 105 kDa molecular mass protein from cell extracts and identified it as human nucleolin. Medium-affinity interactions ( approximately 240 nm) between Lf and purified nucleolin were further illustrated by surface plasmon resonance assays. The interaction of Lf with the cell surface-expressed nucleolin was then demonstrated through competitive binding studies between Lf and the anti-human immunodeficiency virus pseudopeptide, HB-19, which binds specifically surface-expressed nucleolin independently of proteoglycans. Interestingly, binding competition studies between HB-19 and various Lf derivatives in proteoglycan-deficient hamster cells suggested that the nucleolin-binding site is located in both the N- and C-terminal lobes of Lf, whereas the basic N-terminal region is dispensable. On intact cells, Lf co-localizes with surface nucleolin and together they become internalized through vesicles of the recycling/degradation pathway by an active process. Morever, a small proportion of Lf appears to translocate in the nucleus of cells. Finally, the observations that endocytosis of Lf is inhibited by the HB-19 pseudopeptide, and the lack of Lf endocytosis in proteoglycan-deficient cells despite Lf binding, point out that both nucleolin and proteoglycans are implicated in the mechanism of Lf endocytosis

Coronin 1C promotes triple-negative breast cancer invasiveness through regulation of MT1-MMP traffic and invadopodia function

Membrane type 1-matrix metalloproteinase (MT1-MMP), a membrane-tethered protease, is key for matrix breakdown during cancer invasion and metastasis. Assembly of branched actin networks by the Arp2/3 complex is required for MT1-MMP traffic and formation of matrix-degradative invadopodia. Contrasting with the well-established role of actin filament branching factor cortactin in invadopodia function during cancer cell invasion, the contribution of coronin-family debranching factors to invadopodia-based matrix remodeling is not known. Here, we investigated the contribution of coronin 1C to the invasive potential of breast cancer cells. We report that expression of coronin 1C is elevated in invasive human breast cancers, correlates positively with MT1-MMP expression in relation with increased metastatic risk and is a new independent prognostic factor in breast cancer. We provide evidence that, akin to cortactin, coronin 1C is required for invadopodia formation and matrix degradation by breast cancer cells lines and for 3D collagen invasion by multicellular spheroids. Using intravital imaging of orthotopic human breast tumor xenografts, we find that coronin 1C accumulates in structures forming in association with collagen fibrils in the tumor microenvironment. Moreover, we establish the role of coronin 1C in the regulation of positioning and trafficking of MT1-MMP-positive endolysosomes. These results identify coronin 1C as a novel player of the multi-faceted mechanism responsible for invadopodia formation, MT1-MMP surface exposure and invasiveness in breast cancer cells