CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage

The central nervous system (CNS) contains several types of immune cells located in specific anatomic compartments. Macrophages reside at the CNS borders surrounding the brain vessels, in leptomeningeal spaces and the choroid plexus, where they interact with the vasculature and play immunological surveillance and scavenging functions. We investigated the phenotypic changes and role of these macrophages in response to acute ischemic stroke. Given that CD163 expression is a hallmark of perivascular and meningeal macrophages in the rat and human brain, we isolated CD163+ brain macrophages by fluorescence activated cell sorting. We obtained CD163+ cells from control rats and 16 h following transient middle cerebral artery occlusion, after verifying that infiltration of CD163+ peripheral myeloid cells is negligible at this acute time point. Transcriptome analysis of the sorted CD163+ cells identified ischemia-induced upregulation of the hypoxia inducible factor-1 pathway and induction of genes encoding for extracellular matrix components and leukocyte chemoattractants, amongst others. Using a cell depletion strategy, we found that CNS border-associated macrophages participate in granulocyte recruitment, promote the expression of vascular endothelial growth factor (VEGF), increase the permeability of pial and cortical blood vessels, and contribute to neurological dysfunction in the acute phase of ischemia/reperfusion. We detected VEGF expression surrounding blood vessels and in some CD163+ perivascular macrophages in the brain tissue of ischemic stroke patients deceased one day after stroke onset. These findings show ischemia-induced reprogramming of the gene expression profile of CD163+ macrophages that has a rapid impact on leukocyte chemotaxis and blood-brain barrier integrity, and promotes neurological impairment in the acute phase of stroke

Tumour-derived CSF2/granulocyte macrophage colony stimulating factor controls myeloid cell accumulation and progression of gliomas

BACKGROUND: Malignant tumours release factors, which attract myeloid cells and induce their polarisation to pro-invasive, immunosuppressive phenotypes. Brain-resident microglia and peripheral macrophages accumulate in the tumour microenvironment of glioblastoma (GBM) and induce immunosuppression fostering tumour progression. Macrophage colony stimulating factors (CSFs) control the recruitment of myeloid cells during peripheral cancer progression, but it is disputable, which CSFs drive their accumulation in gliomas. METHODS: The expression of CSF2 (encoding granulocyte-macrophage colony stimulating factor) was determined in TCGA datasets and five human glioma cell lines. Effects of stable CSF2 knockdown in glioma cells or neutralising CSF2 or receptor CSF2Rα antibodies on glioma invasion were tested in vitro and in vivo. RESULTS: CSF2 knockdown or blockade of its signalling reduced microglia-dependent glioma invasion in microglia-glioma co-cultures. CSF2-deficient human glioma cells encapsulated in cell-impermeable hollow fibres and transplanted to mouse brains, failed to attract microglia, but stimulated astrocyte recruitment. CSF2-depleted gliomas were smaller, attracted less microglia and macrophages, and provided survival benefit in tumour-bearing mice. Apoptotic microglia/macrophages were detected in CSF2-depleted tumours. CONCLUSIONS: CSF2 is overexpressed in a subset of mesenchymal GBMs in association with high immune gene expression. Tumour-derived CSF2 attracts, supports survival and induces pro-tumorigenic polarisation of microglia and macrophages

Zmiany histologiczne w plucach myszy wywolane doswiadczalnym zakazeniem pelzakami z grupy "limax"

The studies revealed that the infection with the „limax" group amoebae resulted in the severe changes in the respiratory system: in interstitial pneumonia, the injuries of the bronchi, the bronchioles and the blood vessels. The histopathological examinations showed the focal destruction of the alveoli in case of the mild amoeba invasion while the massive invasion caused the complete destruction of the respiratory epithelium, the blood vessels, the bronchi and the bronchioles. Apart from all the changes in the alveoli, in most cases the significant pulmonary hyperaemia and the numerous blood foci were observed. Moreover, the histopathological changes in the blood vessels, the bronchi and the bronchioles consisting in the epithelial destruction and the laceration of the blood vessel walls and the bronchioles were disclosed

THE HISTOPATHOLOGICAL CHANGES IN THE LUNGS OF MICE EXPERIMENTALLY INFECTED WITH AMOEBAE OF THE „LIMAX” GROUP

The studies revealed that the infection with the „limax" group amoebae resulted in the severe changes in the respiratory system: in interstitial pneumonia, the injuries of the bronchi, the bronchioles and the blood vessels. The histopathological examinations showed the focal destruction of the alveoli in case of the mild amoeba invasion while the massive invasion caused the complete destruction of the respiratory epithelium, the blood vessels, the bronchi and the bronchioles. Apart from all the changes in the alveoli, in most cases the significant pulmonary hyperaemia and the numerous blood foci were observed. Moreover, the histopathological changes in the blood vessels, the bronchi and the bronchioles consisting in the epithelial destruction and the laceration of the blood vessel walls and the bronchioles were disclosed

Struktura mozga sinantropnykh mukh iz semejjstva Tabanidae

The paper deals with the histological structure of the brain in the specimens of the Tabanidae family including Tabanus, Chrysops and Chrysosona genera. Measurements of the brain volume and of the brain cen tres were made and the ratio of the size of the centres to that of the brain was given on the example of the female of Tabanus bromius. Lobi olfactorii are the best developed brain centres in Tabanidae. They take up 88.53% of the whole brain in the female of Tabanus bromius. Corpora pedunculata are poorly developed (0.14%) and built up of single, small calyces and thin stalks. The central body is well developed and consists of three parts. The central body takes up 0.15% of the size of the brain in the female of Tabanus bromius. Although lobi olfactorii are small when compared with the size of the brain (0.29%), the size of the antennal glomerules and thick fibres of the antenno-globular tracts are an evidence of a well developed sense of smell in those parasites

Myeloid-derived suppressor cells in gliomas

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of early myeloid progenitors and precursors at different stages of differentiation into granulocytes, macrophages, and dendritic cells. Blockade of their differentiation into mature myeloid cells in cancer results in an expansion of this population. High-grade gliomas are the most common malignant tumours of the central nervous system (CNS), with a poor prognosis despite intensive radiation and chemotherapy. Histopathological and flow cytometry analyses of human and rodent experimental gliomas revealed the extensive heterogeneity of immune cells infiltrating gliomas and their microenvironment. Immune cell infiltrates consist of: resident (microglia) and peripheral macrophages, granulocytes, myeloid-derived suppressor cells, and T lymphocytes. Intratumoural density of glioma-associated MDSCs correlates positively with the histological grade of gliomas and patient’s survival. MDSCs have the ability to attract T regulatory lymphocytes to the tumour, but block the activation of tumour-reactive CD4+ T helper cells and cytotoxic CD8+ T cells. Immunomodulatory mechanisms employed by malignant gliomas pose an appalling challenge to brain tumour immunotherapy. In this mini-review we describe phenotypic and functional characteristics of MDSCs in humans and rodents, and their occurrence and potential roles in glioma progression. While understanding the complexity of immune cell interactions in the glioma microenvironment is far from being accomplished, there is significant progress that may lead to the development of immunotherapy for gliomas

Electrophoretic characteristics of soluble proteins of Fasciola hepatica (Linnaeus, 1758)

Proteins were extracted from F. hepatica collected on cattle and sheep. The extract was purified in the column with sephadex G-25. The proteins were separated using the Davis method in electrophoretic systems constructed by the authors, in the columns and in blocks in polyacrylamid gel. The electrophoregrams served for making densometric diagrams and for calculating electrophoretic mobility coefficient (Rf) of the identified protein bands. Both in the blocks and in the columns 26 protein bands have been identified in F. hepatica from both cattle and sheep. Statistical analysis with t Student test showed significant differences in their Rf values. A high reproducibility of the results has been obtained both in the columns and in the blocks of polyacrilamid gel