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Results for “Extracellular vesicles”

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At least 415 records · Page 23Linked to original sources

PubMed1986

Secretory cells in the nucleus pulposus of the adult human intervertebral disc. A preliminary report.

A light microscopical study was conducted to ascertain the type of cells in the nucleus pulposus of the adult human intervertrebral disc. Three lumbar intervertebral discs were removed from each of 15 male and female adults at autopsy (ages ranged from 19 to 62 years). The tissue was fixed in formalin, decalcified in formic acid, dehydrated in a graded series of ethanol, embedded in paraffin, and serially sectioned at 7-10 micron. Tissue sections were affixed to albuminized glass slides and stained either by hematoxylin and eosin or hematoxylin and Van Gieson's stain. The cells of the bulk of the nucleus pulposus consisted of chondrocytes and a few fibroblasts; however, the subchondral matrix of the nucleus pulposos contained numerous stellate cells with (from 1 to 8) unusually long (up to 80 micron) primary cytoplasmic processes that often branch into secondary processes. The cell processes contained cytoplasmic varicosities at various intervals along their lengths; and their endings often expanded into bulbous, vesicle-filled process terminals. The surrounding extracellular matrix usually contained numerous, vesicle-filled, eosinophil matrix bodies. Morphological similarities of cytoplasmic varicosities, process terminals, and matrix bodies, as well as the apparent budding of process terminals, suggest that these previously unidentified cells are secreting an unknown matrix component into the subchondral matrix of the nucleus pulposus of the adult human.

Adult↗

PubMed1988

Morphological and immunocytochemical studies of fibronectin-coated, plasma membrane-limited vesicles in the early chicken embryo.

Vesticles with a mean outside diameter of 32.8 nm have been observed in the early chicken embryo after fixation with a mixture of glutaraldehyde and tannic acid. Densitometric tracing has revealed that the vesicles are limited by a unit membrane. The presence of complex carbohydrates is suggested by the increased electron density of the vesticles after addition of tannic acid to the fixative. Immunocytochemical staining with a monoclonal antibody directed against chicken cellular fibronectin demonstrated the presence of this glycoprotein along the surface of the vesicles. These results suggest a cellular origin of the vesicles, since their surface shares morphological and biochemical similarities with the cell surfaces of the embryonic tissue layers. Recycling of plasma-membrane vesicles may occur, as vesicles were found in the vicinity of coated vesicles. We postulate that extracellular materials of the cell surface, which may affect cell and tissue interactions, are shed in the environment together with plasma-membrane vesicles. The difficulties encountered in observing the vesicles stems from the facts that an adequate visualization method is necessary and that they are few in number. The latter reason suggests their transient nature. The vesicles probably rapidly disintegrate in the extracellular milieu or are recycled by the cell surface.

Animals↗

PubMed1984

Microangiopathy of vasa nervorum in dysglobulinemic neuropathy.

Thickening of vessel walls resulting from endothelial proliferation was observed in the vasa nervorum of eleven patients with peripheral neuropathy associated with dysglobulinemia. Electron microscopy showed endothelial proliferation accompanied by abnormal accumulation of masses of intracytoplasmic filaments in each case. Of the eleven patients with dysglobulinemia, nine had monoclonal gammopathy and two were found to have polyclonal elevation of gamma globulin levels. Symptoms of neuropathy characteristically preceded detection of serum protein abnormalities by months to years. Nerve fiber lesions involved primarily the axon in four cases; segmental demyelination was the principal abnormality in the other seven. Both abnormalities were present to some degree in all eleven patients. Biphasic myelinopathy with uniform separation of myelin lamellae attributable to globulin deposition was observed in four cases. The microvascular changes included endothelial cytoplasmic enlargement, virtually obliterating the vessel lumen in many instances, with thickening of pericytes, in which intracytoplasmic filaments were prominent and pinocytotic vesicles numerous. No extracellular filaments were noted, and amyloid stains were negative. Possible effects of these microvascular changes include ischemia resulting from severe vascular luminal narrowing, and altered vascular permeability. Severe loss of axons in this group of neuropathies may be the result of ischemia, whereas altered vascular permeability may admit globulin into the endoneurium, where it may directly affect the myelin sheath and precipitate demyelination.

Adult↗

PubMed2003

Intracellular zinc fluxes associated with apoptosis in growth plate chondrocytes.

Matrix vesicles released by epiphyseal growth plate chondrocytes are known to contain a significant quantity of labile Zn(2+). Zonal analysis of chicken metatarsal bones showed that the resting/proliferative region of the growth plate contained high levels of Zn(2+) with significantly lower levels in the hypertrophic cartilage suggesting a loss of cellular Zn(2+) as the chondrocytes mature. Intracellular labile Zn(2+) was measured in primary cultures of growth plate chondrocytes by assay with the fluorescent Zn-chelator toluenesulfonamidoquinoline (TSQ) and imaged by multi-photon laser scanning microscopy (MPLSM) with the TSQ derivative zinquin. Short-term exposure to Zn(2+), both in the presence and absence of pyrithione resulted in significant increases in cytosolic Zn(2+). Treatment with the membrane-permeant Zn(2+) chelator TPEN rapidly reduced the levels of labile Zn(2+) and triggered apoptosis. Cytosolic Zn(2+) levels were significantly reduced following 24-h incubations with known inducers of chondrocyte apoptosis. The loss of intracellular Zn(2+) was accompanied by a significant reduction in the cytosolic metal-binding protein metallothionein. Examination of Zn(2+)-treated cells with MPLSM showed uniformly higher zinquin fluorescence. Treatment of Zn(2+)-loaded cells with TPEN quenched zinquin fluorescence confirming that the observed fluorescence in chondrocytes is due to the presence of intracellular Zn(2+). A dose-dependent increase in zinquin fluorescence was observed in cells treated with a range of Zn(2+) concentrations. Short-term treatment of cultured chondrocytes with apoptosis-inducing chemicals resulted in transient increases in intracellular labile Zn(2+). These results indicate that Zn(2+) is mobilized from intracellular binding sites in the early stages of chondrocyte apoptosis and is subsequently lost from the cells. The early mobilization of Zn(2+) provides a mechanism for its movement to matrix vesicles and the extracellular matrix.

Animals↗

PubMed1995

Outer membrane-associated deoxyribonuclease activity of Porphyromonas gingivalis.

Extracellular outer membrane vesicles which are produced by Gram-negative bacteria may enclose deoxyribonucleic acid (DNA). While characterizing vesicles of Porphyromonas gingivalis, it was found that they do not contain detectable amount of DNA. It was also shown that the presence of deoxyribonuclease activity on whole cells and vesicles can degrade plasmidic and linear DNA. Deoxyribonuclease activity was also demonstrated in several other Gram-negative oral bacterial species. The nuclease activity of P. gingivalis was further characterized. When deoxyribonuclease activity was analyzed by zymography, only one active band was detected under the conditions tested. This nuclease enzyme showed a molecular weight of approximately 50 kDa. The activity was inhibited by 5 mM ZnCl2 or 100 mM EDTA whereas Mg2+ or Ca2+ ions were not required for activity. Activity was totally destroyed by treatment at 70 degrees C for 15 min. Although the enzyme may participate in virulence or provide nucleic acid precursors for bacterial growth, its exact role is still unknown.

Journal Article↗

PubMed1987

Effect of cooling on intracellular transport and secretion of thyroglobulin.

The effect of cooling to 20 degrees C on the intracellular transport and secretion of thyroglobulin was studied by incubating open thyroid follicles isolated from porcine thyroid tissue. Follicles were labeled with 3H-leucine or 3H-galactose and the secretion of labeled thyroglobulin into the incubation medium was followed by chase incubations under various experimental conditions. The observations indicate that the transport of thyroglobulin is inhibited at three sites of the intracellular pathway by cooling to 20 degrees C, i.e., between the RER cisternae and the Golgi cisternae, between the latter and the exocytic vesicles, and between these vesicles and the extracellular space (corresponding to the follicle lumen). The secretion of 3H-leucine-labeled thyroglobulin decreased linearly between 37 degrees and 20 degrees C; within this temperature range the activation energy for secretion, calculated from Arrhenius plots, was found to be 37 kcal/mol. Below 20 degrees C the secretion was scarcely measurable. It is suggested that the three transport blocks at 20 degrees C result mainly from inhibition of membrane fission and fusion due to phase transition in membrane lipids.

Animals↗

PubMed1986

Ultrastructural demonstration of secretion by exocytosis in rat pinealocytes with the use of the tannic acid method.

In the rat pineal gland the mechanism of release of secretory material was studied ultrastructurally after incubating tissues in Ringer solution containing tannic acid. The results indicate that pinealocytes release the contents of secretory vesicles into the extracellular space via exocytosis, a phenomenon that has not been visualized previously in this cell type. This finding may reflect release of polypeptides by the pineal gland.

Animals↗

PubMed1986

Experimental tympanosclerosis following infection with Streptococcus pyogenes and vitamin D3 intoxication.

A rat animal model was used to study the ultrastructure of submucosal calcifications induced in the middle ear following inoculation with Streptococcus pyogenes and high doses of parenteral vitamin D3. The morphological changes present in affected animals resembled the classical picture of tympanosclerosis. While calcification occurred about bacterial remnants and myelin structures, the most important calcification centers were lysosomal and non-lysosomal matrix vesicles in the extracellular spaces. These formed band-like calcifications close to the basal membrane without affecting the epithelial layer. This animal model offers the possibility of studying the effect of various therapeutic regimens in the treatment of the dynamic tympanosclerotic process.

Animals↗

PubMed1991

Biphasic cellular response to transection in the newt optic nerve: glial reactivity precedes axonal degeneration.

Morphological interactions between axons and glia within the lesioned newt optic nerve were studied at time periods prior to the onset of Wallerian degeneration. Optic nerves were transected 0.5 mm from the eye, animals were killed at 5, 10, 20 and 30 min post-lesion, and the intracranial half of the tract was examined with light and electron microscopy. A sequence of structural changes was observed within the time interval 5-30 min post-lesion. Over the first 20 minutes these changes primarily involved the endogenous neuroglia; there was a displacement of glial nuclei from the center to the periphery of the nerve and an increase of 50-100% in glial cytoplasmic and nuclear area. Nuclei of reactive glia were euchromatic and surrounded by a high density of Golgi, vesicles, mitochondria and filaments, the last of which extended throughout the expanded glial processes. Optic axons appear intact at 20 min post-lesion except for some separation between the axolemma and myelin sheath in some of the myelinated fibres. By 30 min post-lesion both myelinated and non-myelinated fibres were found in various stages of lysis. Many of the expanded glial processes contained a population of vesicles aggregated adjacent to the glial plasmalemma. Profiles of infolded glial membranes suggested the opening of such vesicles into the extracellular space around degenerating axons. We conclude that, after optic nerve injury, there are very rapid reactive changes in glia and axons, with the changes in glia preceding the degenerative events in axons.

Animals↗

PubMed1996

Plasma membrane fragility in dystrophic neurites in senile plaques of Alzheimer's disease: an index of oxidative stress.

This study presents evidence for plasma membrane abnormalities of the dystrophic neurites in senile plaques of Alzheimer's disease. We found that the plasma membranes of dystrophic neurites are more labile to fixation than those membranes of other cells of the senile plaque or of normal neurites distant from senile plaques. Further, we found vesicles in the extracellular space adjacent to dystrophic neurites and similar to those within them, suggesting that the increased lability seen in our preparations may, in vivo, be associated with release of neuritic contents. Plasma membrane alterations may be critical to deposition of amyloid-beta in senile plaques from the abundant beta-protein precursor of dystrophic neurites. The consequences of altered membrane integrity, such as calcium influx, lipid peroxidation and free radical damage, could also be responsible for many of the pathological correlates of the disease.

Alzheimer Disease↗

PubMed1996

Vesiculation induced by amphiphiles and ionophore A23187 in porcine platelets: a transmission electron microscopic study.

Amphiphiles, known to induce exo- and endovesiculation in human erythrocytes, were studied by means of transmission electron microscopy (TEM) for their ability to induce shedding of vesicles (microparticles) from the porcine platelet plasma membrane. While echinocytogenic amphiphiles induced shedding of vesicles to the extracellular medium (exovesiculation), stomatocytogenic amphiphiles did not induce endovesiculation. The rapid (< 1 min) formation of many thin spicules in platelets upon treatment with echinocytogenic amphiphiles, indicates that spicule-formation is caused by a primary interaction of the amphiphile with the plasma membrane. Agonist- (Ca(2+)-ionophore A23187, thrombin and collagen) induced shape changes, however, seem to involve contractile cytoskeletal processes since treated cells attained heavily irregular shapes with broad pseudopods. Our study indicates that the mechanisms involved in amphiphile- and agonist-induced exovesiculation differ. Amphiphile-induced exovesicles are mainly electron-dense spherical structures (phi 150-200 nm) which originate from the formed spicules. Ionophore A23187-induced exovesicles are large (phi 200-800 nm) predominantly electron-lucent structures which are mainly shed from the cell body and seem to originate from extrusions of the canalicular system. Our study shows that there are several similarities but also obvious differences in the response of platelets and erythrocytes to amphiphile-treatment.

Animals↗

PubMed1989

The low density lipoprotein receptor.

The study of familial hypercholesterolemia at the molecular level has led to its advancement from a clinical syndrome to a fascinating experimental system. FH was first described 50 years ago by Carl Müller who concluded that the disease produces high plasma cholesterol levels and myocardial infarctions in young people, and is transmitted as an autosomal dominant trait determined by a single gene. The existence of two forms of FH, namely heterozygous and homozygous, was recognized by Khachadurian and Fredrickson and Levy much later. The value of FH as an experimental model system lies in the availability of homozygotes, because mutant genes can be studied without interference from the normal gene. The first and most important breakthrough was the realization that the defect underlying FH could be studied in cultured skin fibroblasts. Rapidly, the LDL receptor pathway was conceptualized and its dysfunction in cells from FH homozygotes was demonstrates. Isolation of the normal LDL receptor protein and studies on the biosynthesis and structure of abnormal receptors in mutant cell lines provided essential groundwork for elucidation of defects at the DNA level. The power of the experimental system, FH, became nowhere more obvious than in work that correlated structural information at the protein level with the elucidation of defined defects in the LDL receptor gene. In addition to revealing important structure-function relationships in the LDL receptor polypeptide and delineating mutational events, studies of FH have established several more general concepts. First, the tight coupling of LDL binding to its internalization suggested that endocytosis was not a non-specific process as suggested from early observations. The key finding was that LDL receptors clustered in coated pits, structures that had been described by Roth and Porter 10 years earlier. These investigators had demonstrated, in electron microscopic studies on the uptake of yolk proteins by mosquito oocytes, that coated pits pinch off from the cell surface and form coated vesicles that transport extracellular fluid into the cell. Studies on the LDL receptor system showed directly that receptor clustering in coated pits is the essential event in this kind of endocytosis, and thus established receptor-mediated endocytosis as a distinct mechanism for the transport of macromolecules across the plasma membrane. Subsequently, many additional systems of receptor-mediated endocytosis have been defined, and variations of the overall pathway have been described.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

PubMed2004

Fusion pore dynamics are regulated by synaptotagmin*t-SNARE interactions.

Exocytosis involves the formation of a fusion pore that connects the lumen of secretory vesicles with the extracellular space. Exocytosis from neurons and neuroendocrine cells is tightly regulated by intracellular [Ca2+] and occurs rapidly, but the molecular events that mediate the opening and subsequent dilation of fusion pores remain to be determined. A putative Ca2+ sensor for release, synaptotagmin I (syt), binds directly to syntaxin and SNAP-25, which are components of a conserved membrane fusion complex. Here, we show that Ca2+-triggered syt*SNAP-25 interactions occur rapidly. The tandem C2 domains of syt cooperate to mediate binding to syntaxin/SNAP-25; lengthening the linker that connects C2A and C2B selectively disrupts this interaction. Expression of the linker mutants in PC12 cells results in graded reductions in the stability of fusion pores. Thus, the final step of Ca2+-triggered exocytosis is regulated, at least in part, by direct contacts between syt and SNAP-25/syntaxin.

Animals↗

PubMed1993

Biological functions of entactin.

Entactin is a sulfated multidomain glycoprotein component of basement membranes. The molecule consists of 1217 amino acids which are organized into two terminal globular domains linked by a rod-like structure largely composed of four EGF- and one thyroglobulin-like cysteine-rich homology repeats. Entactin binds to laminin, collagen IV, fibrinogen, and fibronectin. In the parietal endoderm M1536-B3 cell line, the laminin-entactin complex is formed intracellularly and transported in membrane enclosed vesicles to the extracellular compartment. Transfection of human choriocarcinoma JAR cells, which do not synthesize entactin, with entactin cDNA results in the synthesis and insertion of entactin into the extracellular matrix where it becomes associated with laminin and collagen IV. Indirect immunofluorescent staining also reveals that entactin co-localizes with fibronectin in the extracellular matrix of the embryonal carcinoma-derived 4CQ cell line. These observations suggest that entactin plays an important role in the assembly and properties of diverse extracellular matrices. In addition, entactin binds to immobilized fibrinogen, and more specifically, to the A alpha and B beta chains. The binding of radiolabeled entactin to immobilized fibrinogen is not dependent on metal ions, and is inhibited by antibodies against either fibrinogen or entactin, soluble fibrinogen, and unlabeled entactin. This interaction combined with the chemotactic and phagocytic promoting activities of entactin may be important in hemostasis and would healing.

Animals↗

PubMed1967

Electron-opaque bodies and fat droplets in mouse liver after fasting or glucose injection.

Fasting produces an increased mobilization of lipid from adipose tissue to the liver and a decreased hepatic lipogenesis, but the administration of glucose stimulates lipid synthesis by the liver. After fasting of C3H mice numerous electron-opaque bodies and large lipid droplets were present in the liver. In the liver of untreated controls only a few small electron-opaque bodies and an occasional fat droplet were observed. After glucose injection the number of electron-opaque bodies in the liver was no greater than that observed in livers of saline-injected controls. In the livers of all groups these bodies were located intracellularly within cytoplasmic vesicles; those in extracellular locations were not membrane bounded and were located at indented and thickened hepatocyte plasma membranes or within the space of Disse. In fasted liver the dense bodies were often associated with large fat droplets.

Adipose Tissue↗

PubMed1976

Ultrastructural study of lesions induced in rabbit cornea by Herpes Simplex virus types 1 and 2.

Herpes simplex virus types 1 and 2 were used to infect rabbit corneas (without abrasion), and the resulting lesions were compared by light and electron microscopy. The type 1-induced lesion developed more quickly; the infected epithelial cells underwent a progression of defined morphological changes leading to organelle destruction, cell rounding, and death. Virus particles were abundant in the nuclei and cytoplasm of all types of cell in the epithelium, in intercellular spaces, and on the basement membrane. Occasionally, virus was seen to replicate within stromal fibroblasts. In contrast, type 2, although causing similar changes in the epithelial cells, was relatively inefficient in the production of mature virions. Thus type 2 nucleocapsids were synthesized within nuclei in numbers comparable to those of types 1, but intact cytoplasmic virions were uncommon, apparently because of degradation of type 2 virions in cytoplasmic vesicles or tubules. Extracellular type 2 particles were rarely seen. This finding offers an explanation for the relatively slow development of the type 2-induced lesion, but not for its greater severity. All epithelial cells appeared to be capable of supporting replication of either type of virus.

Animals↗

PubMed1991

Ultrastructural localization of factor VIII-related antigen in endothelial proliferations of malignant gliomas.

The ultrastructural localization of Factor VIII-related antigen (FVIII/RAg) in the endothelial cells of malignant gliomas was studied with immunogold labelling on thin sections of LR White-embedded tissue. FVIII/RAg was localized in Weibel-Palade bodies (WPBs) as well as in cytoplasmic vacuoles and vesicles, and in extracellular spaces. Stained WPBs were found both in cells surrounding vascular channels and in several proliferating cells of solid buds and glomeruli. Our results confirm previous ultrastructural observations on non-neural tissues that FVIII/RAg is produced by endothelial cells and stored in WPBs. The presence of FVIII/RAg-stained WPBs in capillary buds and tufts indicates that at least some of the proliferating cells are endothelial in origin rather than pericytes. Thus, the contribution of endothelial cells to new vessel formation seems to be more substantial than previously reported.

Antigens↗

PubMed1978

Fine structure of the cell surface and Golgi apparatus of Ochromonas.

Ochromonas danica has an unusually flexible cell surface capable of producing projections of varying sizes and shapes: large projections, 340-360 nm long, and small projections, 50-110 nm long. These projections have been demonstrated by transmission and scanning electron microscopy; some of them may break off into the medium and be the source of extracellular membranes and vesicles reported in the cell-free O. danica growth medium. Ruthernium red stained the acid mucopolysaccharide layer just outside the cell surface as well as small blebs at the cell surface. The Golgi complex of O. danica, Ochromonas malhamensis, Ochromonas sociabilis and Ochromonas sp. produced small coated vesicles which may move toward and fuse with the plasma membrane. The role of the several vesicles is unknown but possible functions are discussed.

Animals↗