Search results for "MACRO"
showing 10 items of 3471 documents
Spontaneous lymphokine synthesis by human blood mononuclear cells
1975
LYMPHOCYTES, after antigenic stimulation, may synthesise and release biologically active soluble factors other than antibodies. These mediators were termed lymphokines by Dumonde1, and the most extensively studied and best characterised are migration inhibitory factors which can inhibit the migration of macrophages or leukocytes: this is the property used for their in vitro bioassay. Apart from antigens, various other stimuli may trigger lymphokine synthesis by lymphocytes, for example, polyclonal mitogens2, anti-immunoglobulin or membrane Fc or C3-receptor reactions3,4. Furthermore, migration inhibitory activity has been found in the long term culture supernatants of some established lymph…
Circulating specific antibodies enhance systemic cross-priming by delivery of complexed antigen to dendritic cells in vivo
2012
Increasing evidence suggests that antibodies can have stimulatory effects on T-cell immunity. However, the contribution of circulating antigen-specific antibodies on MHC class I cross-priming in vivo has not been conclusively established. Here, we defined the role of circulating antibodies in cross-presentation of antigen to CD8(+) T cells. Mice with hapten-specific circulating antibodies, but naϊve for the T-cell antigen, were infused with haptenated antigen and CD8(+) T-cell induction was measured. Mice with circulating hapten-specific antibodies showed significantly enhanced cross-presentation of the injected antigen compared with mice that lacked these antibodies. The enhanced cross-pre…
Microglia in CNS development: Shaping the brain for the future
2017
Microglial cells are the resident macrophages of the central nervous system (CNS) and are mainly known for their roles in neuropathologies. However, major recent developments have revealed that these immune cells actively interact with neurons in physiological conditions and can modulate the fate and functions of synapses. Originating from myeloid precursors born in the yolk sac, microglial cells invade the CNS during early embryonic development. As a consequence they can potentially influence neuronal proliferation, migration and differentiation as well as the formation and maturation of neuronal networks, thereby contributing to the entire shaping of the CNS. We review here recent evidenc…
Gray Matter NG2 Cells Display Multiple Ca2+-Signaling Pathways and Highly Motile Processes
2011
NG2 cells, the fourth type of glia in the mammalian CNS, receive synaptic input from neurons. The function of this innervation is unknown yet. Postsynaptic changes in intracellular Ca(2+)-concentration ([Ca(2+)](i)) might be a possible consequence. We employed transgenic mice with fluorescently labeled NG2 cells to address this issue. To identify Ca(2+)-signaling pathways we combined patch-clamp recordings, Ca(2+)-imaging, mRNA-transcript analysis and focal pressure-application of various substances to identified NG2-cells in acute hippocampal slices. We show that activation of voltage-gated Ca(2+)-channels, Ca(2+)-permeable AMPA-receptors, and group I metabotropic glutamate-receptors provo…
Role of Sortilin in Models of Autoimmune Neuroinflammation
2015
Abstract The proneurotrophin receptor sortilin is a protein with dual functions, being involved in intracellular protein transport, as well as cellular signal transduction. The relevance of the receptor for various neuronal disorders, such as dementia, seizures, and brain injury, is well established. In contrast, little is known about the role of sortilin in immune cells and inflammatory diseases. The aim of our study was to elucidate the distribution of sortilin in different immune cell types in mice and humans and to analyze its function in autoimmune CNS inflammation. Sortilin was expressed most profoundly in murine and human macrophages and dendritic cells and to a much lesser extent in…
Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System
2015
SummaryDuring early embryogenesis, microglia arise from yolk sac progenitors that populate the developing central nervous system (CNS), but how the tissue-resident macrophages are maintained throughout the organism’s lifespan still remains unclear. Here, we describe a system that allows specific, conditional ablation of microglia in adult mice. We found that the microglial compartment was reconstituted within 1 week of depletion. Microglia repopulation relied on CNS-resident cells, independent from bone-marrow-derived precursors. During repopulation, microglia formed clusters of highly proliferative cells that migrated apart once steady state was achieved. Proliferating microglia expressed …
Inclusion complexes of Cethyl-2-methylresorcinarene and pyridine N-oxides: breaking the C–I⋯−O–N+ halogen bond by host–guest complexation
2016
C ethyl-2-Methylresorcinarene forms host–guest complexes with aromatic N-oxides through multiple intra- and intermolecular hydrogen bonds and C–H⋯π interactions. The host shows conformational flexibility to accommodate 3-methylpyridine N-oxide, while retaining a crown conformation for 2-methyl- and 4-methoxypyridine N-oxides highlighting the substituent effect of the guest. N-Methylmorpholine N-oxide, a 6-membered ring aliphatic N-oxide with a methyl at the N-oxide nitrogen, is bound by the equatorial −N–CH3 group located deep in the cavity. 2-Iodopyridine N-oxide is the only guest that manifests intermolecular N–O⋯I–C halogen bond interactions, which are broken down by the host resulting i…
Scorpiand-like azamacrocycles prevent the chronic establishment of Trypanosoma cruzi in a murine model.
2013
Chagas disease is today one of the most important neglected diseases for its upcoming expansion to non-endemic areas and has become a threat to blood recipients in many countries. In this study, the trypanocidal activity of ten derivatives of a family of aza-scorpiand like macrocycles is evaluated against Trypanosoma cruzi in vitro and in vivo murine model in which the acute and chronic phases of Chagas disease were analyzed. The compounds 4, 3 and 1 were found to be more active against the parasite and less toxic against Vero cells than the reference drug benznidazole, 4 being the most active compound, particularly in the chronic phase. While all these compounds showed a remarkable degree …
Synthesis and inhibitory activity of dimethylamino-chalcone derivatives on the induction of nitric oxide synthase.
2002
A series of nine dimethylamino-chalcone derivatives (1,3-diaryl-propenones) was synthesized and screened as potential inhibitors of NO and PGE(2) production in the RAW 264.7 macrophage cell line. 4-Dimethylamino-2',5'-dimethoxychalcone (6) was found to be the most potent and dual inhibitor (IC(50s) in the submicromolar range) of NO and PGE(2) production. 2',6'-Dimethoxylation appeared to be an effective requirement for selective and potent inhibition of nitric oxide synthase induction as it was confirmed by Western blot analysis. Chalcone (6) at 25 mg kg(-1) by oral route, inhibited significantly the formation of oedema in the carrageenan-induced model of inflammation in mice.
Phenylsulphonyl urenyl chalcone derivatives as dual inhibitors of cyclo-oxygenase-2 and 5-lipoxygenase
2005
Two series of phenylsulphonyl urenyl chalcone derivatives (UCH) with various patterns of substitution were tested for their effects on nitric oxide (NO) and prostaglandin E2 (PGE2) overproduction in RAW 264.7 macrophages. None of the tested compounds reduced NO production more than 50% at 10 microM but most of them inhibited the generation of PGE2 with IC50 values under the micromolar range. Me-UCH 1, Me-UCH 5, Me-UCH 9, Cl-UCH 1, and Cl-UCH 9 were selected to evaluate their influence on human leukocyte functions and eicosanoids generation. These derivatives selectively inhibited cyclo-oxygenase-2 (COX-2) activity in human monocytes being Me-UCH 5 the most potent (IC50 0.06 microM). Selecte…