Dataset Information

Localization of blood proteins thrombospondin1 and ADAMTS13 to cerebral corpora amylacea.

ABSTRACT: Corpora amylacea (CA) have long been described in aging brains and in patients with neurodegenerative conditions, but their origins have been debated. It has been proposed that CA represent collections of nervous system breakdown products that accumulate within astrocytic cytoplasm. In support of this, studies have shown that CA include glycosylated material, ubiquitin, and an assortment of proteins derived from neuronal cytoplasm. On the other hand, many of these proteins are not specifically localized to neurons or astrocytes; some components of CA, such as complement proteins, are most abundantly expressed outside the central nervous system. The characteristic predilection for CA to accumulate near vessels and ependyma suggests that proteins extravasated from blood or transudated from CSF may form a component of these structures. In this study, we report the immunohistochemical localization of blood and platelet proteins thrombospondin1 and ADAMTS13 in CA from aged individuals and patients with vascular dementia. Thrombospondin1 localized to neurons, but was most prominently localized to CA. An independent serum and platelet expressed protein, ADAMTS13, was found in CA in the same brain regions. In vitro analysis shows that thrombospondin1 and ADAMTS13 form complexes together in cells and in direct protein binding assays. We speculate that CA could result from a conglomeration of interacting proteins from degenerating neurons and from extravasated blood elements released after transient breakdown of the blood-brain barrier.

SUBMITTER: Meng H

PROVIDER: S-EPMC2871975 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Localization of blood proteins thrombospondin1 and ADAMTS13 to cerebral corpora amylacea.

Meng He H Zhang Xiaojie X Blaivas Mila M Wang Michael M MM

Neuropathology : official journal of the Japanese Society of Neuropathology 20090428 6

Corpora amylacea (CA) have long been described in aging brains and in patients with neurodegenerative conditions, but their origins have been debated. It has been proposed that CA represent collections of nervous system breakdown products that accumulate within astrocytic cytoplasm. In support of this, studies have shown that CA include glycosylated material, ubiquitin, and an assortment of proteins derived from neuronal cytoplasm. On the other hand, many of these proteins are not specifically l ...[more]

PMID: 19422532

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Project description:BackgroundCorpora amylacea of human brain, recently renamed as wasteosomes, are granular structures that appear during aging and also accumulate in specific areas of the brain in neurodegenerative conditions. Acting as waste containers, wasteosomes are formed by polyglucosan aggregates that entrap and isolate toxic and waste substances of different origins. They are expelled from the brain to the cerebrospinal fluid (CSF), and can be phagocytosed by macrophages. In the present study, we analyze the phagocytosis of wasteosomes and the mechanisms involved in this process. Accordingly, we purified wasteosomes from post-mortem extracted human CSF and incubated them with THP-1 macrophages. Immunofluorescence staining and time-lapse recording techniques were performed to evaluate the phagocytosis. We also immunostained human hippocampal sections to study possible interactions between wasteosomes and macrophages at central nervous system interfaces.ResultsWe observed that the wasteosomes obtained from post-mortem extracted CSF are opsonized by MBL and the C3b complement protein. Moreover, we observed that CD206 and CD35 receptors may be involved in the phagocytosis of these wasteosomes by THP-1 macrophages. Once phagocytosed, wasteosomes become degraded and some of the resulting fractions can be exposed on the surface of macrophages and interchanged between different macrophages. However, brain tissue studies show that, in physiological conditions, CD206 but not CD35 receptors may be involved in the phagocytosis of wasteosomes.ConclusionsThe present study indicates that macrophages have the machinery required to process and degrade wasteosomes, and that macrophages can interact in different ways with wasteosomes. In physiological conditions, the main mechanism involve CD206 receptors and M2 macrophages, which trigger the phagocytosis of wasteosomes without inducing inflammatory responses, thus avoiding tissue damage. However, altered wasteosomes like those obtained from post-mortem extracted CSF, which may exhibit waste elements, become opsonized by MBL and C3b, and so CD35 receptors constitute another possible mechanism of phagocytosis, leading in this case to inflammatory responses.

Project description:BackgroundCorpora amylacea are amyloid bodies commonly found adjacent to damaged prostate epithelium. Little is known about their formation or function. The current study sought to characterize corpora amylacea in prostate tissue and to describe their relationship with clinical, histological, molecular, and lifestyle factors, especially with chronic inflammation which is associated with aggressive disease.MethodsWe studied a cohort of 355 men with prostate cancer and tissue specimens from the Health Professionals Follow-Up Study. Pathologists examined H&E slides and undertook a standardized review for histologic data and inflammation. Trained observers counted corpora amylacea within the benign and predominately tumor areas. Immunohistochemistry biomarkers were available from tissue microarrays. We used multivariable logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) to assess associations of chronic inflammation, clinical, histological, molecular, and lifestyle factors with the presence of corpora amylacea.ResultsCorpora amylacea were present in benign tissue area for 298 men (84%). Specimens with moderate-to-severe chronic inflammation were more likely to have corpora amylacea in benign regions (OR = 5.4 95%CI 1.9, 15.6). Moreover, corpora amylacea were more common in men with higher body mass index (OR = 1.13 95%CI 1.01, 1.26). In contrast, Gleason grade (OR = 0.4 95%CI 0.2, 0.8), proliferation index (OR = 0.6 95%CI 0.3, 1.2) and the presence of the TMPRSS2:ERG fusion (OR = 0.4 95%CI 0.2, 0.8) were inversely associated with corpora amylacea presence. TURP specimens were less likely to have corpora amylacea than prostatectomy specimens (OR = 0.12 95%CI 0.03, 0.47). Age, PSA, stage, biomarkers of angiogenesis and PTEN, and vasectomy were not significantly associated with corpora amylacea.ConclusionCorpora amylacea were common among men with prostate cancer and were associated with pro-inflammatory factors, some markers of less aggressive disease, and lack of the TMPRSS2:ERG fusion.

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Localization of blood proteins thrombospondin1 and ADAMTS13 to cerebral corpora amylacea.

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Localization of blood proteins thrombospondin1 and ADAMTS13 to cerebral corpora amylacea.

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