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Background: Acute pancreatitis is an inflammation of the pancreatic glandular parenchyma that causes injury with or without the destruction of pancreatic acini. Clinical and experimental evidence suggest that certain systemic proinflammatory mediators may be responsible for initiating the fundamental mechanisms involved in microglial reactivity. Here, we investigated the possible repercussions of acute pancreatitis (AP) on the production of inflammatory mediators in the brain parenchyma focusing on microglial activation in the hippocampus., Methods: The acute pancreatic injury in rats was induced by a pancreas ligation surgical procedure (PLSP) on the splenic lobe, which corresponds to approximately 10% of total mass of the pancreas. Blood samples were collected via intracardiac puncture for the measurement of serum amylase. After euthanasia, frozen or paraffin-embedded brains and pancreas were analyzed using qRT-PCR or immunohistochemistry, respectively., Results: Immunohistochemistry assays showed a large number of Iba1 and PU.1-positive cells in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus of the PLSP group. TNF-α mRNA expression was significantly higher in the brain from PLSP group. NLRP3 inflammasome expression was found to be significantly increased in the pancreas and brain of rats of the PLSP group. High levels of BNDF mRNA were found in the rat brain of PLSP group. In contrast, NGF mRNA levels were significantly higher in the control group versus PLSP group., Conclusion: Our findings suggest that AP has the potential to induce morphological changes in microglia consistent with an activated phenotype., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Olfactory ensheathing cells (OECs) are a type of specialized glial cell currently considered as having a double function in the nervous system: one regenerative, and another immune. Streptococcus pneumoniae is a major agent of severe infections in humans, including meningitis. It is commonly found in the nasopharynx of asymptomatic carriers, and, under certain still unknown conditions, can invade the brain. We evaluated whether pneumococcal cells recovered from lysed OECs and microglia are able to survive by manipulating the host cell activation. An intracellular-survival assay of S. pneumoniae in OECs showed a significant number of bacterial CFU recovered after 3 h of infection. In contrast, microglia assays resulted in a reduced number of CFU. Electron-microscopy analysis revealed a large number of pneumococci with apparently intact morphology. However, microglia cells showed endocytic vesicles containing only bacterial cell debris. Infection of OEC cultures resulted in continuous NF-κB activation. The IFN-γ-induced increase of iNOS expression was reversed in infected OECs. OECs are susceptible to S. pneumoniae infection, which can suppress their cytotoxic mechanisms in order to survive. We suggest that, in contrast to microglia, OECs might serve as safe targets for pneumococci, providing a more stable environment for evasion of the immune system.

Intra-abdominal adhesions are major post-operative complications for which no effective means of prevention is available. We aimed to evaluate the efficacy of exogenous pulmonary surfactant administration in the prevention of post-operative abdominal adhesions. Rats were randomly assigned to undergo laparotomy (L) or gastroenterostomy (GE) and then treated with surfactant (groups L-S and GE-S, respectively). Intra-abdominal adhesions, collagen fibre content, metalloproteinase (MMP)-9, expression of growth factors (TGF-β, KGF and VEGF), type III procollagen (PCIII) and pro-caspase 3, as well as isolectin B4 and ED1-positive cells expressing MMP-9, were evaluated. Groups treated with surfactant (GE-S and L-S) exhibited fewer adhesions. A significant reduction in collagen fibre content was observed in GE-S compared to GE animals (P < 0.001). In situ and gelatin zymography analysis showed higher MMP-9 expression and activity in the GE-S group compared to the GE group (P < 0.05). ED1-positive cell counts were significantly higher in the GE-S group (P < 0.001) than in the GE group. Virtually all cells positive for ED1 were MMP-9+. Double-labelling of MMP-9 with IB4 showed no significant differences between GE-S and GE groups. TGF-β, KGF, PCIII and pro-caspase-3 mRNA expression decreased significantly in GE-S compared to GE animals (P < 0.05). Surfactant administration also reduced apoptosis in the GE-S group. These findings suggest that surfactant reduces the intra-abdominal adhesions triggered by laparotomy and gastrointestinal anastomosis, thus preventing fibrosis formation at the peritoneal surfaces. This preclinical study suggests an innovative treatment strategy for intra-abdominal adhesions with surfactant and to endorse its putative mechanism of action., (© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: The ability of S. pneumoniae to generate infections depends on the restrictions imposed by the host's immunity, in order to prevent the bacterium from spreading from the nasopharynx to other tissues, such as the brain. Some authors claim that strains of S. pneumoniae, which fail to survive in the bloodstream, can enter the brain directly from the nasal cavity by axonal transport through the olfactory and/or trigeminal nerves. However, from the immunological point of view, glial cells are far more responsive to bacterial infections than are neurons. This hypothesis is consistent with several recent reports showing that bacteria can infect glial cells from the olfactory bulb and trigeminal ganglia. Since our group previously demonstrated that Schwann cells (SCs) express a functional and appropriately regulated mannose receptor (MR), we decided to test whether SCs are involved in the internalization of S. pneumoniae via MR., Results: Immediately after the interaction step, as well as 3 h later, the percentage of association was approximately 56.5%, decreasing to 47.2% and 40.8% after 12 and 24 h, respectively. Competition assays by adding a 100-fold excess of mannan prior to the S. pneumoniae infection reduced the number of infected cells at 3 and 24 h. A cytochemistry assay with Man/BSA-FITC binding was performed in order to verify a possible overlap between mannosylated ligands and internalized bacteria. Incubation of the SCs with Man/BSA-FITC resulted in a large number of intracellular S. pneumoniae, with nearly complete loss of the capsule. Moreover, the anti-pneumococcal antiserum staining colocalized with the internalized man/BSA-FITC, suggesting that both markers are present within the same endocytic compartment of the SC., Conclusions: Our data offer novel evidence that SCs could be essential for pneumococcal cells to escape phagocytosis and killing by innate immune cells. On the other hand, the results also support the idea that SCs are immunocompetent cells of the PNS that can mediate an efficient immune response against pathogens via MR.

The use of bone marrow mononuclear cells (BMMCs) has been shown as a putative efficient therapy for stroke. However, the mechanisms of therapeutic action are not yet completely known. Mannose receptor (MR) is a subgroup of the C-type lectin receptor superfamily involved in innate immune response in several tissues. Although known primarily for its immune function, MR also has important roles in cell migration, cell debris clearance and tissue remodeling during inflammation and wound healing. Here we analyzed MR expression in brains of rats one week after induction of unilateral focal cortical ischemia by thermocoagulation in blood vessels of sensorimotor cortex. Additionally, we evaluated possible changes in such expression in cortices of rats subjected to ischemia plus treatment with BMMCs. Our results showed high expression of MR in an unknown GFAP(+) cell type and in phagocytic macrophages/microglia within the lesion boundary zone whereas in the non-injured (contralateral) cortical parenchyma, low levels of MR expression were observed. Moreover, therapy with BMMCs induced overexpression of MR in ipsilateral (injured) cortex. Previous studies from our group have shown functional recovery and decreased neurodegeneration in BMMC-treated rats in the same model of focal cortical ischemia. Thus, we suggest that ischemic injury induces large increase in MR expression as part of a mechanism for clearance of damage-associated molecular patterns (DAMPs). In addition, induction of MR overexpression by BMMCs might increase the efficiency of clearance, being one of the protective mechanisms of these cells., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Olfactory ensheathing cells (OECs) are a special glia that ensheath olfactory receptor axons that enter the brain via olfactory phila, thus, providing a potential route for access of pathogens. Streptococcus pneumoniae (Sp), that has a capsule rich in mannosyl residues, is the most common cause of rhinosinusitis that may evolve to meningitis. We have tested whether OECs in vitro express the mannose receptor (MR), and could internalize Sp via MR. Cultures were infected by a suspension of Sp (ATCC 49619), recognized by an anti-Sp antibody, in a 100:1 bacteria:cells ratio. Competition assays, by means of mannan, showed around a 15-fold reduction in the number of internalized bacteria. To verify whether MR could be involved in Sp uptake, OECs were reacted with an antibody against the MR C-terminal peptide (anti-cMR) and bacteria were visualized with Sytox Green. Selective cMR-immunoreaction was seen in perinuclear compartments containing bacteria whereas mannan-treated cultures showed an extremely low percentage of internalized bacteria and only occasional adhered bacteria. Our data suggest the involvement of MR in adhesion of bacteria to OEC surface, and in their internalization. Data are also coherent with a role of OECs as a host cell prior to (and during) bacterial invasion of the brain., (Copyright © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)