We showed that, after infection via the bloodstream, early granulomas were formed in the brain parenchyma and the ventricular system of both embryos and in larvae containing a fully developed BBB. Our experiments with Tg(Fli1:GFP)y1 casper embryos confirmed these findings and indicated that mycobacteria leave the bloodstream and are able to establish new granulomas in surrounding tissue; because individuals with an intact BBB do develop TBM, it is clear that mycobacteria traverse this barrier. However, the exact mechanism is not yet known.. The BBB consists of endothelial cells with tight junctions, surrounded by a continuous basement membrane and astroglial end-feet (Abbott et al., 2006), which limits the exchange of pathogens, pharmacological compounds, immune cells and mediators (Ransohoff et al., 2003). Three major mechanisms of traversal across this BBB are described for other causative pathogens of meningitis: transcellular migration, paracellular migration or the Trojan-horse mechanism ...

TY - JOUR. T1 - Invasion of the central nervous system by Cryptococcus neoformans requires a secreted fungal metalloprotease. AU - Vu, Kiem. AU - Tham, Rick. AU - Uhrig, John P.. AU - Thompson, George R.. AU - Na Pombejra, Sarisa. AU - Jamklang, Mantana. AU - Bautos, Jennifer M.. AU - Gelli, Angie. PY - 2014/6/3. Y1 - 2014/6/3. N2 - Cryptococcus spp. cause life-threatening fungal infection of the central nervous system (CNS), predominantly in patients with a compromised immune system. Why Cryptococcus neoformans has this remarkable tropism for the CNS is not clear. Recent research on cerebral pathogenesis of C. neoformans revealed a predominantly transcellular migration of cryptococci across the brain endothelium; however, the identities of key fungal virulence factors that function specifically to invade the CNS remain unresolved. Here we found that a novel, secreted metalloprotease (Mpr1) that we identified in the extracellular proteome of C. neoformans (CnMpr1) is required for establishing ...

Intracellular fluid, as its name suggests, is found inside the cells in the human organism. Extracellular fluid, on the other hand, is outside the cell; it is comprised of the interstitial, intravascular and transcellular compartments.

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In this study we demonstrate that ROI are also able to indirectly mediate PMN activation via oxidative modification of selected serum proteins to conformations that bind to and activate PMN. Because prominent ROI release is a common feature of many pathological conditions, this protein-dependent pathway of PMN activation may represent an enhancer mechanism of inflammation.. In recent years data have accumulated on the contribution of ROI to the development of various disease states, such as ARDS (16, 21), atherosclerosis (17), chronic obstructive pulmonary disease (18), sepsis (24), or side effects of hemodialysis (20, 29) and mAb treatment (19). The therapeutically used anti-CD3 mAb OKT3 strongly induces the neutrophil oxidative burst in a strictly IgG2a-dependent FcγR-mediated fashion (19). It was speculated that this massive ROI release could be involved in the frequently occurring first dose effects of OKT3, characterized by adhesive activation of PMN and sequestration in the pulmonary ...

Persistence of bacteria in spite of a normal host immune system and relevant antibiotic treatment is a key problem in many chronic infections, such as the bronchopulmonary P. aeruginosa infection in cystic fibrosis patients. The capability of bacteria to establish themselves in microcolonies or biof …

In the study to evaluate the anti-inflammatory potential of a series of trihydroxyflavones by testing their ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cells and cell-free systems and to inhibit the proinflammatory pathways mediated by the enzymes cyclooxygenase (COX) and 5-lipoxygenase (5-LOX), in which reactive species have a proven involvement, showed that The tested trihydroxyflavones proved to be effective inhibitors of neutrophils oxidative burst and were shown to scavenge different ROS and RNS in cell-free systems. The most active compound in the majority of the assays was 3,3,4-trihydroxyflavone, which was somehow expected due to the presence of the ortho-dihydroxy in the B-ring, an important structural feature in terms of free radical scavenging activity and the compounds were able to inhibit the production of leukotriene B(4) by 5-LOX in activated neutrophils. 3,5,7-Trihydroxyflavone was able to inhibit both COX-1 and COX-2, which makes ...