Search results for: APOLD1 VERGE
#19524662 
2009/06/12
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How T-cell-dependent and -independent challenges access the brain: vascular and neural responses to bacterial lipopolysaccharide and staphylococcal enterotoxin B.
Bacterial lipopolysaccharide (LPS) is widely used to study immune influences on the CNS, and cerebrovascular prostaglandin (PG) synthesis is implicated in mediating LPS influences on some acute phase responses. Other bacterial products, such as staphylococcal enterotoxin B (SEB), impact target tissues differently in that their effects are T-lymphocyte-dependent, yet both LPS and SEB recruit a partially overlapping set of subcortical central autonomic cell groups. We sought to compare neurovascular responses to the two pathogens, and the mechanisms by which they may access the brain. Rats received iv injections of LPS (2 microg/kg), SEB (1mg/kg) or vehicle and were sacrificed 0.5-3h later. Both challenges engaged vascular cells as early 0.5h, as evidenced by induced expression of the vascular early response gene (Verge), and the immediate-early gene, NGFI-B. Cyclooxygenase-2 (COX-2) expression was detected in both endothelial and perivascular cells (PVCs) in response to LPS, but only in PVCs of SEB-challenged animals. The non-selective COX inhibitor, indomethacin (1mg/kg, iv), blocked LPS-induced activation in a subset of central autonomic structures, but failed to alter SEB-driven responses. Liposome mediated ablation of PVCs modulated the CNS response to LPS, did not affect the SEB-induced activational profile. By contrast, disruptions of interoceptive signaling by area postrema lesions or vagotomy (complete or hepatic) markedly attenuated SEB-, but not LPS-, stimulated central activational responses. Despite partial overlap in their neuronal and vascular response profiles, LPS and SEB appear to use distinct mechanisms to access the brain.Jordi Serrats, Paul E Sawchenko
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Verge: a novel vascular early response gene.
Vascular endothelium forms a continuous, semipermeable barrier that regulates the transvascular movement of hormones, macromolecules, and other solutes. Here, we describe a novel immediate early gene that is expressed selectively in vascular endothelial cells, verge (vascular early response gene). Verge protein includes an N-terminal region of approximately 70 amino acids with modest homology (approximately 30% identity) to Apolipoprotein L but is otherwise unique. Verge mRNA and protein are induced selectively in the endothelium of adult vasculature by electrical or chemical seizures. Verge expression appears to be responsive to local tissue conditions, because it is induced in the hemisphere ipsilateral to transient focal cerebral ischemia. In contrast to the transient expression in adult, Verge mRNA and protein are constitutively expressed at high levels in the endothelium of developing tissues (particularly heart) in association with angiogenesis. Verge mRNA is induced in cultured endothelial cells by defined growth factors and hypoxia. Verge protein is dramatically increased by cysteine proteinase inhibitors, suggesting rapid turnover, and is localized to focal regions near the periphery of the cells. Endothelial cell lines that stably express Verge form monolayers that show enhanced permeability in response to activation of protein kinase C by phorbol esters. This response is accompanied by reorganization of the actin cytoskeleton and the formation of paracellular gaps. These studies suggest that Verge functions as a dynamic regulator of endothelial cell signaling and vascular function.Jean B Regard, Sigrid Scheek, Talaibek Borbiev, Anthony A Lanahan, Armin Schneider, Anna-Maria Demetriades, Holger Hiemisch, Carol A Barnes, Alexander D Verin, Paul F Worley