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Decreased Infiltration (decreased + infiltration)
Selected AbstractsAltered immune response to CNS viral infection in mice with a conditional knock-down of macrophage-lineage cellsGLIA, Issue 2 2006Jessica Carmen Abstract Neuroadapted Sindbis Virus (NSV) is a neuronotropic virus that causes hindlimb paralysis in susceptible mice and rats. The authors and others have demonstrated that though death of infected motor neurons occurs, bystander death of uninfected neurons also occurs and both contribute to the paralysis that ensues following infection. The authors have previously shown that the treatment of NSV-infected mice with minocycline, an inhibitor that has many functions within the central nervous system (CNS), including inhibiting microglial activation, protects mice from paralysis and death. The authors, therefore, proposed that microglial activation may contribute to bystander death of motor neurons following NSV infection. Here, the authors tested the hypothesis using a conditional knock-out of activated macrophage-lineage cells, including endogenous CNS macrophage cells. Surprisingly, ablation of these cells resulted in more rapid death and similar weakness in the hind limbs of NSV-infected animals compared with that of control animals. Several key chemokines including IL-12 and monocyte chemoattractant protein-1 (MCP-1) did not become elevated in these animals, resulting in decreased infiltration of T lymphocytes into the CNS of the knock-down animals. Either because of the decreased macrophage activation directly or because of the reduced immune cell influx, viral replication persisted longer within the nervous system in knock-down mice than in wild type mice. The authors, therefore, conclude that although macrophage-lineage cells in the CNS may contribute to neurodegeneration in certain situations, they also serve a protective role, such as control of viral replication. © 2006 Wiley-Liss, Inc. [source] CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis,HEPATOLOGY, Issue 4 2010Mirko Moreno Zaldivar Liver fibrosis is a major cause of morbidity and mortality worldwide. Platelets are involved in liver damage, but the underlying molecular mechanisms remain elusive. Here, we investigate the platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) as a molecular mediator of fibrotic liver damage. Serum concentrations and intrahepatic messenger RNA of CXCL4 were measured in patients with chronic liver diseases and mice after toxic liver injury. Platelet aggregation in early fibrosis was determined by electron microscopy in patients and by immunohistochemistry in mice. Cxcl4,/, and wild-type mice were subjected to two models of chronic liver injury (CCl4 and thioacetamide). The fibrotic phenotype was analyzed by histological, biochemical, and molecular analyses. Intrahepatic infiltration of immune cells was investigated by fluorescence-activated cell sorting, and stellate cells were stimulated with recombinant Cxcl4 in vitro. The results showed that patients with advanced hepatitis C virus,induced fibrosis or nonalcoholic steatohepatitis had increased serum levels and intrahepatic CXCL4 messenger RNA concentrations. Platelets were found directly adjacent to collagen fibrils. The CCl4 and thioacetamide treatment led to an increase of hepatic Cxcl4 levels, platelet activation, and aggregation in early fibrosis in mice. Accordingly, genetic deletion of Cxcl4 in mice significantly reduced histological and biochemical liver damage in vivo, which was accompanied by changes in the expression of fibrosis-related genes (Timp-1 [tissue inhibitor of matrix metalloproteinase 1], Mmp9 [matrix metalloproteinase 9], Tgf -, [transforming growth factor beta], IL10 [interleukin 10]). Functionally, Cxcl4,/, mice showed a strongly decreased infiltration of neutrophils (Ly6G) and CD8+ T cells into the liver. In vitro, recombinant murine Cxcl4 stimulated the proliferation, chemotaxis, and chemokine expression of hepatic stellate cells. Conclusion: The results underscore an important role of platelets in chronic liver damage and imply a new target for antifibrotic therapies. (HEPATOLOGY 2010.) [source] Effects of urbanization on streamflow in the Atlanta area (Georgia, USA): a comparative hydrological approachHYDROLOGICAL PROCESSES, Issue 8 2001Seth Rose Abstract For the period from 1958 to 1996, streamflow characteristics of a highly urbanized watershed were compared with less-urbanized and non-urbanized watersheds within a 20 000 km2 region in the vicinity of Atlanta, Georgia: in the Piedmont and Blue Ridge physiographic provinces of the southeastern USA. Water levels in several wells completed in surficial and crystalline-rock aquifers were also evaluated. Data were analysed for seven US Geological Survey (USGS) stream gauges, 17 National Weather Service rain gauges, and five USGS monitoring wells. Annual runoff coefficients (RCs; runoff as a fractional percentage of precipitation) for the urban stream (Peachtree Creek) were not significantly greater than for the less-urbanized watersheds. The RCs for some streams were similar to others and the similar streams were grouped according to location. The RCs decreased from the higher elevation and higher relief watersheds to the lower elevation and lower relief watersheds: values were 0·54 for the two Blue Ridge streams, 0·37 for the four middle Piedmont streams (near Atlanta), and 0·28 for a southern Piedmont stream. For the 25 largest stormflows, the peak flows for Peachtree Creek were 30% to 100% greater than peak flows for the other streams. The storm recession period for the urban stream was 1,2 days less than that for the other streams and the recession was characterized by a 2-day storm recession constant that was, on average, 40 to 100% greater, i.e. streamflow decreased more rapidly than for the other streams. Baseflow recession constants ranged from 35 to 40% lower for Peachtree Creek than for the other streams; this is attributed to lower evapotranspiration losses, which result in a smaller change in groundwater storage than in the less-urbanized watersheds. Low flow of Peachtree Creek ranged from 25 to 35% less than the other streams, possibly the result of decreased infiltration caused by the more efficient routing of stormwater and the paving of groundwater recharge areas. The timing of daily or monthly groundwater-level fluctuations was similar annually in each well, reflecting the seasonal recharge. Although water-level monitoring only began in the 1980s for the two urban wells, water levels displayed a notable decline compared with non-urban wells since then; this is attributed to decreased groundwater recharge in the urban watersheds due to increased imperviousness and related rapid storm runoff. Copyright © 2001 John Wiley & Sons, Ltd. [source] Amelioration of experimental autoimmune encephalomyelitis in Lewis rats treated with fucoidanPHYTOTHERAPY RESEARCH, Issue 3 2010Heechul Kim Abstract We examined whether fucoidan affected the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in rats. EAE was induced in Lewis rats that were immunized with guinea-pig myelin basic protein (MBP) and complete Freund's adjuvant. Fucoidan (50,mg/kg, daily) was administered to rats with EAE intraperitoneally, either in the EAE induction phase from either 1 day before immunization to day 7 post-immunization (PI), or the effector phase from day 8 to 14 PI, to test which phase of rat EAE is affected by fucoidan treatment. The onset, severity and duration of EAE paralysis in the fucoidan-treated group in the days 8,14 PI-treated rats, but not in days ,1,7 PI-treated rats, were significantly delayed, suppressed and reduced, respectively, compared with the vehicle-treated controls. Treatment with fucoidan reduced the encephalitogenic response and TNF-, production during EAE. Moreover, the clinical amelioration coincided with decreased infiltration of inflammatory cells in the EAE-affected spinal cord. The ameliorative effect of fucoidan on clinical paralysis in EAE-affected rats may be mediated, in part, by the suppression of the autoreactive T cell response and inflammatory cytokine production. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||