Search results for "Triggering"
showing 10 items of 25 documents
TREM-1 ligand expression on platelets enhances neutrophil activation
2007
Abstract The triggering receptor expressed on myeloid cells 1 (TREM-1) plays an important role in the innate immune response related to severe infections and sepsis. Modulation of TREM-1–associated activation improves the outcome in rodent models for pneumonia and sepsis. However, the identity and occurrence of the natural TREM-1 ligands are so far unknown, impairing the further understanding of the biology of this receptor. Here, we report the presence of a ligand for TREM-1 on human platelets. Using a recombinant TREM-1 fusion protein, we demonstrate specific binding of TREM-1 to platelets. TREM-1–specific signals are required for the platelet-induced augmentation of polymorphonuclear leu…
Distinct Signaling Cascades of TREM-1, TLR and NLR in Neutrophils and Monocytic Cells
2013
Triggering receptor expressed on myeloid cells 1 (TREM-1) is an important mediator of innate inflammatory responses in microbial infections and sepsis. TREM-1 ligation on neutrophils (PMN) or monocytes results in the production of proinflammatory cytokines. Engagement of TREM-1 induces the activation of MAP kinases as well as rapid Ca<sup>2+</sup> mobilization. However, a detailed understanding of TREM-1 signaling pathways is currently lacking. We evaluated the TREM-1 signaling hierarchy in monocytic cells and found that the acute myeloid leukemia cell line MUTZ-3 expresses TREM-1 in a natural and functional manner. We compared essential signaling molecules of the TREM-1, TLR an…
Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus.
2005
Human cytomegalovirus, a chief pathogen in immunocompromised people, can persist in a healthy immunocompetent host throughout life without being eliminated by the immune system. Here we show that pp65, the main tegument protein of human cytomegalovirus, inhibited natural killer cell cytotoxicity by an interaction with the activating receptor NKp30. This interaction was direct and specific, leading to dissociation of the linked CD3zeta from NKp30 and, consequently, to reduced killing. Thus, pp65 is a ligand for the NKp30 receptor and demonstrates a unique mechanism by which an intracellular viral protein causes general suppression of natural killer cell cytotoxicity by specific interaction w…
Human NK cells selective targeting of colon cancer-initiating cells: a role for natural cytotoxicity receptors and MHC class I molecules
2013
Abstract Tumor cell populations have been recently proposed to be composed of two compartments: tumor-initiating cells characterized by a slow and asymmetrical growth, and the “differentiated” cancer cells with a fast and symmetrical growth. Cancer stem cells or cancer-initiating cells (CICs) play a crucial role in tumor recurrence. The resistance of CICs to drugs and irradiation often allows them to survive traditional therapy. NK cells are potent cytotoxic lymphocytes that can recognize tumor cells. In this study, we have analyzed the NK cell recognition of tumor target cells derived from the two cancer cell compartments of colon adenocarcinoma lesions. Our data demonstrate that freshly p…
Influence of the Madden-Julian Oscillation on Southern African summer rainfall
2007
Rain-causing mechanisms over Southern Africa (south of 15˚S) involve both tropical and temperate dynamics. Most studies focused on the synoptical timescale, while the intraseasonal (20-120 days) variability has more been neglected to date. This study aims at determining whether the dominant mode of intraseasonal variability in the Tropics, namely the Madden-Julian Oscillation (MJO), has a significant impact on Southern African rainfall and associated atmospheric dynamics. The examination of outgoing longwave radiation (OLR) over Southern Africa shows indeed significant intraseasonal fluctuations at the 30-60 day timescale, i.e. in the pe- riods that are typically reminiscent of the MJO. In ord…
Exploiting Maximum Entropy method and ASTER data for assessing debris flow and debris slide susceptibility for the Giampilieri catchment (north-easte…
2016
This study aims at evaluating the performance of the Maximum Entropy method in assessing landslide susceptibility, exploiting topographic and multispectral remote sensing predictors. We selected the catchment of the Giampilieri stream, which is located in the north-eastern sector of Sicily (southern Italy), as test site. On 1 October 2009, a storm rainfall triggered in this area hundreds of debris flow/avalanche phenomena causing extensive economical damage and loss of life. Within this area a presence-only-based statistical method was applied to obtain susceptibility models capable of distinguishing future activation sites of debris flow and debris slide, which where the main source of fai…
A multidisciplinary approach to the evaluation of the mechanism that triggered the Cerda landslide (Sicily, Italy).
2005
Abstract The present paper describes a multidisciplinary approach to the evaluation of a seismically triggered landslide that occurred in the Cerda area (Italy) on September 6, 2002, about 1 h after an earthquake took place in the south Tyrrhenian Sea. The study was focused on an analysis of the role of the seismic input in triggering the landslide, in view of the evidence that no other mass movement was recorded in the adjacent areas despite geological and geomorphological spatial homogeneity. The studied area is located on a slope of the western flank of the Fiume Imera Settentrionale (Northern Sicily), which is made up of clayey–arenitic rocks. The slope inclines gently but is not unifor…
Critical limb ischaemia is characterised by an increased production of whole blood reactive oxygen species and expression of TREM-1 on neutrophils
2013
Atherosclerosis is a chronic inflammatory process involving polymorphonuclear neutrophils (PMN) and formation of reactive oxygen species (ROS). The aim of the present study was to investigate the phenotype of inflammatory cells in regard to the expression of triggering receptor expressed on myeloid cells (TREM)-1 and its soluble form (sTREM-1) as well as its relationship with oxidative stress in peripheral artery disease (PAD) patients.In total 90 patients with PAD (N = 30 intermittent claudication (IC)300 m absolute walking distance, N = 30 IC300 m absolute walking distance, N = 30 critical limb ischaemia (CLI)) and 30 control persons were included. ROS formation was measured at basal or s…
Signaling pathways of the TREM-1- and TLR4-mediated neutrophil oxidative burst.
2008
The triggering receptor expressed on myeloid cells 1 (TREM-1) is involved in the innate inflammatory response to microbial infections. Activation and expression of TREM-1 by polymorphonuclear neutrophils (PMN) occurs in concert with Toll-like receptors (TLR) such as TLR4 for bacterial lipopolysaccharide. However, it is currently unclear how this is mediated on a molecular level. Using pharmacological inhibitors and Western blot analysis we demonstrate that phosphatidyl inositide 3-kinase, phospholipase C and the mitogen-activated kinase p38MAPK are essential for the TREM-1- and TLR4-induced oxidative burst of human PMN. The activation of protein kinase B and extracellular signal-related kin…
Using synchrotrons and XFELs for time-resolved X-ray crystallography and solution scattering experiments on biomolecules
2015
International audience; Time-resolved structural information is key to understand the mechanism of biological processes, such as catalysis and signalling. Recent developments in X-ray sources as well as data collection and analysis methods are making routine time-resolved X-ray crystallography and solution scattering experiments a real possibility for structural biologists. Here we review the information that can be obtained from these techniques and discuss the considerations that must be taken into account when designing a time-resolved experiment.