Central Nervous System Injury Triggers Hepatic CC and CXC Chemokine Expression that Is Associated with Leukocyte Mobilization and Recruitment to Both the Central Nervous System and the Liver

The administration of interleukin-1beta to the brain induces hepatic CXC chemokine synthesis, which increases neutrophil levels in the blood, liver, and brain. We now show that such hepatic response is not restricted to the CXC chemokines. CCL-2, a CC chemokine, was released by the liver in response to a tumor necrosis factor (TNF)-alpha challenge to the brain and boosted monocyte levels. Furthermore, a clinically relevant compression injury to the spinal cord triggered hepatic chemokine expression of both types. After a spinal cord injury, elevated CCL-2 and CXCL-1 mRNA and protein were observed in the liver by TaqMan reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay as early as 2 to 4 hours. Simultaneously, we observed elevated levels of these chemokines and circulating leukocyte populations in the blood. Leukocytes were recruited to the liver at this early stage, whereas at the site of challenge in the central nervous system, few were observed until 24 hours. Artificial elevation of blood CCL-2 triggered dose-dependent monocyte mobilization in the blood and enhanced monocyte recruitment to the brain after TNF-alpha challenge. Attenuation of hepatic CCL-2 production with corticosteroids resulted in reduced monocyte levels after the TNF-alpha challenge. Thus, combined production of CC and CXC hepatic chemokines appears to amplify the central nervous system response to injury.Fil: Campbell, Sandra J.. University of Oxford; Reino UnidoFil: Perry, V. Hugh. University of Southampton; Reino UnidoFil: Pitossi, Fernando Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Butchart, Angus G.. University of Oxford; Reino UnidoFil: Chertoff, Mariela Sandra Juana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Waters, Sara. University of Southampton; Reino UnidoFil: Dempster, Robert. University of Oxford; Reino UnidoFil: Anthony, Daniel C.. University of Oxford; Reino Unid

Central Nervous System Injury Triggers Hepatic CC and CXC Chemokine Expression that Is Associated with Leukocyte Mobilization and Recruitment to Both the Central Nervous System and the Liver

The administration of interleukin-1β to the brain induces hepatic CXC chemokine synthesis, which increases neutrophil levels in the blood, liver, and brain. We now show that such hepatic response is not restricted to the CXC chemokines. CCL-2, a CC chemokine, was released by the liver in response to a tumor necrosis factor (TNF)-α challenge to the brain and boosted monocyte levels. Furthermore, a clinically relevant compression injury to the spinal cord triggered hepatic chemokine expression of both types. After a spinal cord injury, elevated CCL-2 and CXCL-1 mRNA and protein were observed in the liver by TaqMan reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay as early as 2 to 4 hours. Simultaneously, we observed elevated levels of these chemokines and circulating leukocyte populations in the blood. Leukocytes were recruited to the liver at this early stage, whereas at the site of challenge in the central nervous system, few were observed until 24 hours. Artificial elevation of blood CCL-2 triggered dose-dependent monocyte mobilization in the blood and enhanced monocyte recruitment to the brain after TNF-α challenge. Attenuation of hepatic CCL-2 production with corticosteroids resulted in reduced monocyte levels after the TNF-α challenge. Thus, combined production of CC and CXC hepatic chemokines appears to amplify the central nervous system response to injury

Mapping ecosystem service and biodiversity changes over 70 years in a rural English county

1. Biodiversity and ecosystem services continue to be compromised by land-use change, which is often focussed on enhancing agricultural production. Assessment of losses would be aided by analyses of temporal changes in the extent and spatial pattern of services and biodiversity. To date, no studies have mapped long-term changes in ecosystem services using historical maps. 2. We mapped changes between the 1930s – before the considerable intensification of land use in the UK starting in the 1940s – and 2000 in climate change amelioration services (carbon storage), provisioning services(agriculture and forestry) and plant species richness (biodiversity) for Dorset, a rural English county. 3. We combined land-use maps (1-ha resolution) with multiple proxies of service delivery for the 10 different Broad Habitats in the region. Biodiversity was mapped using plant survey data from the two time periods. We used bootstrapping to include uncertainty due to the different proxies and Gini coefficients to quantify statistical changes in spatial pattern. 4. Overall, we found significant increases in agricultural provisioning and large losses in biodiversity over the period, which reflect widespread conversion and intensification of land use. We found no change in Dorset’s carbon store, because carbon lost through land-use intensification was balanced by increases in woodland over the 20th century. 5. The carbon storage and the delivery of provisioning services both became more unequally distributed, indicating a change from relatively homogeneous delivery of services to concentration into hotspots. The maps from the year 2000 showed spatial dissociation of hotspots for carbon, provisioning and biodiversity, which suggests that, compared to the 1930s, modern,intensive land use creates conflicts in delivery of multiple services and biodiversity. 6. Synthesis and applications. Detailed maps of historical changes in location-specific service delivery and biodiversity provide valuable information for land-use planning, highlight trade-offs and help to identify drivers. Furthermore, historical maps provide an important baseline to indicate the suitability and potential success of suggested actions, such as habitat restoration, and their relevance to traditional land use. Various frameworks could be informed by our approach, including the ecosystem service aims of the EU biodiversity strategy and the newly created UK Nature Improvement Areas

Altered chemokine expression in the spinal cord and brain contributes to differential interleukin-1beta-induced neutrophil recruitment.

The pattern of neutrophil recruitment that accompanies inflammation in the CNS depends on the site of injury and the stage of development. The adult brain parenchyma is refractory to neutrophil recruitment and associated damage as compared to the spinal cord or juvenile brain. Using quantitative Taqman RT-PCR and enzyme-liked immunosorbent assay (ELISA), we compared mRNA and protein expression of the rat neutrophil chemoattractant chemokines (CINC) in spinal cord and brain of adult and juvenile rats to identify possible association with the observed differences in neutrophil recruitment. Interleukin-1beta (IL-1beta) injection resulted in up-regulated chemokine expression in both brain and spinal cord. CINC-3 mRNA was elevated above CINC-1 and CINC-2alpha, with expression levels for each higher in spinal cord than in brain. By ELISA, IL-1beta induced greater CINC-1 and CINC-2alpha expression compared to CINC-3, with higher protein levels in spinal cord than in brain. In the juvenile brain, significantly higher levels of CINC-2alpha protein were observed in response to IL-1beta injection than in the adult brain following an equivalent challenge. Correspondingly, neutrophil recruitment was observed in the juvenile brain and adult spinal cord, but not in the adult brain. No expression of CINC-2beta mRNA was detected. Thus differential chemokine induction may contribute to variations in neutrophil recruitment in during development and between the different CNS compartments