Extracellular matrix composition and cellular mechanisms of transplant vasculopathy in rat aortic allografts.
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Animals↗
Biomedical subjects
J Thyberg
Publications and source records attributed to J Thyberg.
Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF.
Most endocrine hormones are produced in tissues and organs with permeable microvessels that may provide an excess of hormones to be transported by the blood circulation to the distal target organ. Here, we investigate whether leptin, an endocrine hormone, induces the formation of vascular fenestrations and permeability, and we characterize its angiogenic property in the presence of other angiogenic factors. We provide evidence that leptin-induced new blood vessels are fenestrated. Under physiological conditions, capillary fenestrations are found in the leptin-producing adipose tissue in lean mice. In contrast, no vascular fenestrations were detected in the adipose tissue of leptin-deficient ob/ob mice. Thus, leptin plays a critical role in the maintenance and regulation of vascular fenestrations in the adipose tissue. Leptin induces a rapid vascular permeability response when administrated intradermally. Further, leptin synergistically stimulates angiogenesis with fibroblast growth factor (FGF)-2 and vascular endothelial growth factor (VEGF), the two most potent and commonly expressed angiogenic factors. These findings demonstrate that leptin has another new function-the increase of vascular permeability.
Adipose Tissue↗
Phenotypic modulation of arterial smooth muscle cells is associated with prolonged activation of ERK1/2.
Arterial smooth muscle cells grown in primary culture on a substrate of fibronectin in serum-free medium are converted from a contractile to a synthetic phenotype. This process is dependent on integrin signaling and includes a major structural reorganization with loss of myofilaments and formation of a large secretory apparatus. Functionally, the cells lose their contractility and become competent to migrate, secrete extracellular matrix components, and proliferate in response to growth factor stimulation. Here, it is demonstrated that the mitogen-activated protein kinases ERK1/2 play a vital role in the fibronectin-mediated modification of rat aortic smooth muscle cells. Immunoblotting showed that phosphorylated ERK1/2 (p44/p42) were expressed throughout the period when the change in phenotypic properties of the cells took place. Moreover, phosphorylated ERK1/2 accumulated in the nucleus as revealed by immunocytochemical staining. Additional support for an active role of ERK1/2 in the shift in smooth muscle phenotype was obtained by the finding that PD98059, an inhibitor of the upstream kinase MEK1, potently suppressed both the expression of phosphorylated ERK1/2 and the fine structural rebuilding of the cells. In conclusion, the observations point to an important and multifaceted role of ERK1/2 in the regulation of differentiated properties and growth of vascular smooth muscle cells.
Animals↗
Prediction of amyloid fibril-forming proteins.
In Alzheimer's disease and spongiform encephalopathies proteins transform from their native states into fibrils. We find that several amyloid-forming proteins harbor an alpha-helix in a polypeptide segment that should form a beta-strand according to secondary structure predictions. In 1324 nonredundant protein structures, 37 beta-strands with > or =7 residues were predicted in segments where the experimentally determined structures show helices. These discordances include the prion protein (helix 2, positions 179-191), the Alzheimer amyloid beta-peptide (Abeta, positions 16-23), and lung surfactant protein C (SP-C, positions 12-27). In addition, human coagulation factor XIII (positions 258-266), triacylglycerol lipase from Candida antarctica (positions 256-266), and d-alanyl-d-alanine transpeptidase from Streptomyces R61 (positions 92-106) contain a discordant helix. These proteins have not been reported to form fibrils but in this study were found to form fibrils in buffered saline at pH 7.4. By replacing valines in the discordant helical part of SP-C with leucines, an alpha-helix is found experimentally and by secondary structure predictions. This analogue does not form fibrils under conditions where SP-C forms abundant fibrils. Likewise, when Abeta residues 14-23 are removed or changed to a nondiscordant sequence, fibrils are no longer formed. We propose that alpha-helix/beta-strand-discordant stretches are associated with amyloid fibril formation.
Alzheimer Disease↗
Arteriosclerosis in rat aortic allografts: early changes in endothelial integrity and smooth muscle phenotype.
BACKGROUND: Transplant arteriosclerosis remains a limiting factor for the long-term survival of transplanted organs and effective treatment is lacking. A rat model of aortic allografts was used to analyze this process by electron microscopy and further characterize the phenotypic properties of the cells involved. METHODS: A segment of abdominal aorta was transplanted orthotopically from Fischer to Lewis rats. The animals were killed 1-12 weeks after the operation (four to six rats/group), and the grafts were removed and processed for microscopy. RESULTS: The first changes (1 week) included detachment of endothelial cells, adhesion of degranulating platelets to the subendothelial matrix, and modification of smooth muscle cells in the media. The latter process was distinguished by loss of myofilaments and formation of a prominent endoplasmic reticulum and Golgi complex (shift from contractile to synthetic phenotype). Subsequently, modified smooth muscle cells invaded the intima. In parallel, lymphocytes and monocytes/macrophages infiltrated the intima and adventitia. The neointima grew in size by cell proliferation and production of extracellular matrix (4-8 weeks). Smooth muscle cells and monocytes/macrophages in the neointima and media were also noted to accumulate cytoplasmic lipid droplets and eventually turn into foam cells and die. Within the lipid-rich cell remnants, calcification occurred. Finally (12 weeks), the growth in mass of the intimal lesions ceased and in some places reformation of an endothelial lining was detected. Few viable smooth muscle cells remained in the media and the inflammatory infiltrate in the adventitia was reduced. CONCLUSIONS: These observations highlight the importance of early changes in endothelial integrity and smooth muscle phenotype in the development of allograft vascular disease and form the basis for a partly modified model of the cellular mechanisms in this process.
Animals↗
7beta-hydroxycholesterol induces Ca(2+) oscillations, MAP kinase activation and apoptosis in human aortic smooth muscle cells.
In the present study, we characterize the early cytotoxic effects of 7beta-hydroxycholesterol, a major cytotoxin in oxidized LDL, in human aortic smooth muscle cells. Within a few minutes after addition, 7beta-hydroxycholesterol induced Ca(2+) oscillations with a frequency of approximately 0.3-0.4 min(-1). A few hours later, thapsigargin-sensitive Ca(2+) pools were depleted, indicating that 7beta-hydroxycholesterol perturbs intracellular Ca(2+) homeostasis. The mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 (but not JNK) were activated within 5 min after addition of 7beta-hydroxycholesterol. The side-chain hydroxylated oxysterols 25-hydroxycholesterol and 27-hydroxycholesterol were more potent in inducing apoptosis than 7beta-hydroxycholesterol and cholesterol-5alpha,6alpha-epoxide, as determined by TUNEL staining. Addition of TNFalpha (10 ng/ml) and IFNgamma (20 ng/ml) enhanced the cytotoxicity of oxysterols and potentiated apoptosis. The cytokines alone were not toxic to smooth muscle cells at these concentrations. 25-Hydroxycholesterol and 7beta-hydroxycholesterol but not cholesterol inhibited protein synthesis at 4-8 h as determined by [35S]methionine incorporation assay. Morphologically, oxysterol-induced cell death was characterized by disorganization of the ER and Golgi membranes. The Ca(2+) and ERK signals preceded the ultrastructural changes induced by 7beta-hydroxycholesterol.
Aorta↗
Differences in caveolae dynamics in vascular smooth muscle cells of different phenotypes.
Vascular smooth muscle cells shift between two major differentiated states with distinct morphological and functional properties, a contractile and a synthetic phenotype. Here, primary cultures were used to study caveolae expression and dynamics in these cells. The results demonstrate that caveolae are more numerous and more actively interact with intracellular organelles in contractile than in synthetic cells. Immunohistochemistry showed that caveolin-1 was mainly localized to caveolae in contractile cells and partly shifted to Golgi-associated vesicles in synthetic cells, whereas caveolin-2 chiefly appeared in cytoplasmic vesicles in both cases. Cholera toxin B subunit, a ligand of GM1 ganglioside, was internalized via caveolae and carried to endosomes and Golgi-associated vesicles. In contractile cells, it later moved into Golgi and endoplasmic reticulum (ER) cisternae and thus had access to the entire endocytic and exocytic pathways. In contrast, in synthetic cells, the tracer was restricted to the endocytic pathway. Filipin staining similarly disclosed that cholesterol was more widely distributed in contractile than in synthetic cells, with strong labeling of both caveolae and adjacent ER portions. Although no direct continuity between caveolae and ER was detected, it is suggested that cholesterol and other molecules may be translocated between these compartments. The observed differences in caveolae expression and dynamics are likely to be significant for the differences in proliferative capacity and cholesterol transport between contractile and synthetic smooth muscle cells.
Animals↗
Fucoidan inhibits smooth muscle cell proliferation and reduces mitogen-activated protein kinase activity.
OBJECTIVES AND DESIGN: fucoidan has previously been shown to inhibit the proliferation of arterial smooth muscle cells both in animal models and in vitro. However, the mechanisms behind the anti-proliferative effects of this polysulfated polysaccharide are not known in detail. Here, the inhibitory effect of fucoidan on rat aortic smooth muscle cell proliferation was examined and compared with the effects of heparin after stimulation with fetal calf serum, platelet-derived growth factor BB, basic fibroblast growth factor, heparin-binding epidermal growth factor, and angiotensin II. MATERIALS AND METHODS: the cultures were analysed with respect to cell proliferation and DNA synthesis by cell counting and measurement of(3)H-thymidine incorporation. Phosphorylation of mitogen-activated protein kinase and nuclear translocation of phosphorylated mitogen-activated protein kinase were studied by immunoblotting and immunocytochemistry. RESULTS: fucoidan was shown to be a more potent inhibitor of smooth muscle cell proliferation than heparin. Fucoidan also reduced growth factor-induced activation of mitogen-activated protein kinase and prevented nuclear translocation of phosphorylated mitogen-activated protein kinase. CONCLUSION: fucoidan is a more potent anti-proliferative polysulphated polysaccharide than heparin and may mediate its effects through inhibition of the mitogen-activated protein kinase pathway in a similar manner as heparin.
Angiotensin II↗
STAT6 is required for the regulation of IL-4-induced cytoskeletal events in B cells.
During lymphocyte activation, changes in cell morphology are commonly observed. This reflects cell functions important for the regulation of immune responses such as cell adhesion or cell migration. Notably, IL-4 has been shown to induce adhesion and locomotion in B cells, and we have recently described that IL-4 causes dramatic changes in B cell morphology. Thus, such B cells spread with dendritic cell protrusions and produce microvilli-like structures. The molecular mechanisms by which IL-4 induces these complex changes are currently unknown. Two signal transduction pathways are well described for IL-4, i.e. one involving insulin receptor substrate (IRS)-2 and a Janus kinase (JAK)/ signal transducer and activator of transcription (STAT) pathway mediated by STAT6. In this study we therefore used B cells from STAT6-deficient mice to address the question of a possible STAT6 dependence in IL-4-induced morphology changes. By light and electron microscopy, cell spreading and polarization were found to be severely impaired and microvilli formation was reduced. In contrast, only mild impairment was observed in cell adhesion in B cells from STAT6-deficient mice. Our results show that adhesion can be induced in the absence of STAT6. However, expression of STAT6 is necessary for optimal responses in both cell adhesion and microvilli induction. STAT6 is also essential to allow an IL-4-dependent spreading or polarization response. A possible interpretation of our results is that STAT6-dependent expression of a specific gene or genes is required for IL-4 to affect changes in B cell morphology.
Animals↗
Amyloid fibril formation by pulmonary surfactant protein C.
Lung surfactant protein C (SP-C) is a lipopeptide that contains two fatty acyl (palmitoyl) chains bound via intrinsically labile thioester bonds. SP-C can transform from a monomeric alpha-helix into beta-sheet aggregates, reminiscent of structural changes that are supposed to occur in amyloid fibril formation. SP-C is here shown to form amyloid upon incubation in solution. Furthermore, one patient with pulmonary alveolar proteinosis (PAP, a rare disease where lung surfactant proteins and lipids accumulate in the airspaces) and six healthy controls have been studied regarding presence and composition of amyloid fibrils in the cell-free fraction of bronchoalveolar lavage (BAL) fluid. Abundant amyloid fibrils were found in BAL fluid from the patient with PAP and, in low amounts, in three of the six healthy controls. SDS-insoluble fibrillar material associated with PAP mainly consists of SP-C, in contrast to the fibrils found in controls. Fibrillated SP-C has to a significant extent lost the palmitoyl groups, and removal of the palmitoyl groups in vitro increases the rate of fibril formation.
Adolescent↗
A molecular model of Alzheimer amyloid beta-peptide fibril formation.
Polymerization of the amyloid beta (Abeta) peptide into protease-resistant fibrils is a significant step in the pathogenesis of Alzheimer's disease. It has not been possible to obtain detailed structural information about this process with conventional techniques because the peptide has limited solubility and does not form crystals. In this work, we present experimental results leading to a molecular level model for fibril formation. Systematically selected Abeta-fragments containing the Abeta16-20 sequence, previously shown essential for Abeta-Abeta binding, were incubated in a physiological buffer. Electron microscopy revealed that the shortest fibril-forming sequence was Abeta14-23. Substitutions in this decapeptide impaired fibril formation and deletion of the decapeptide from Abeta1-42 inhibited fibril formation completely. All studied peptides that formed fibrils also formed stable dimers and/or tetramers. Molecular modeling of Abeta14-23 oligomers in an antiparallel beta-sheet conformation displayed favorable hydrophobic interactions stabilized by salt bridges between all charged residues. We propose that this decapeptide sequence forms the core of Abeta-fibrils, with the hydrophobic C terminus folding over this core. The identification of this fundamental sequence and the implied molecular model could facilitate the design of potential inhibitors of amyloidogenesis.
Alzheimer Disease↗
Role of microtubules in the organization of the Golgi complex.
The Golgi complex of mammalian cells is composed of cisternal stacks that function in processing and sorting of membrane and luminal proteins during transport from the site of synthesis in the endoplasmic reticulum to lysosomes, secretory vacuoles, and the cell surface. Even though exceptions are found, the Golgi stacks are usually arranged as an interconnected network in the region around the centrosome, the major organizing center for cytoplasmic microtubules. A close relation thus exists between Golgi elements and microtubules (especially the stable subpopulation enriched in detyrosinated and acetylated tubulin). After drug-induced disruption of microtubules, the Golgi stacks are disconnected from each other, partly broken up, dispersed in the cytoplasm, and redistributed to endoplasmic reticulum exit sites. Despite this, intracellular protein traffic is only moderately disturbed. Following removal of the drugs, scattered Golgi elements move along reassembling microtubules back to the centrosomal region and reunite into a continuous system. The microtubule-dependent motor proteins cytoplasmic dynein and kinesin bind to Golgi membranes and have been implicated in vesicular transport to and from the Golgi complex. Microinjection of dynein heavy chain antibodies causes dispersal of the Golgi complex, and the Golgi complex of cells lacking cytoplasmic dynein is likewise spread throughout the cytoplasm. In a similar manner, kinesin antibodies have been found to inhibit Golgi-to-endoplasmic reticulum transport in brefeldin A-treated cells and scattering of Golgi elements along remaining microtubules in cells exposed to a low concentration of nocodazole. The molecular mechanisms in the interaction between microtubules and membranes are, however, incompletely understood. During mitosis, the Golgi complex is extensively reorganized in order to ensure an equal partitioning of this single-copy organelle between the daughter cells. Mitosis-promoting factor, a complex of cdc2 kinase and cyclin B, is a key regulator of this and other events in the induction of cell division. Cytoplasmic microtubules depolymerize in prophase and as a result thereof, the Golgi stacks become smaller, disengage from each other, and take up a perinuclear distribution. The mitotic spindle is thereafter put together, aligns the chromosomes in the metaphase plate, and eventually pulls the sister chromatids apart in anaphase. In parallel, the Golgi stacks are broken down into clusters of vesicles and tubules and movement of protein along the exocytic and endocytic pathways is inhibited. Using a cell-free system, it has been established that the fragmentation of the Golgi stacks is due to a continued budding of transport vesicles and a concomitant inhibition of the fusion of the vesicles with their target membranes. In telophase and after cytokinesis, a Golgi complex made up of interconnected cisternal stacks is recreated in each daughter cell and intracellular protein traffic is resumed. This restoration of a normal interphase morphology and function is dependent on reassembly of a radiating array of cytoplasmic microtubules along which vesicles can be carried and on reactivation of the machinery for membrane fusion.
Animals↗
Amyloid beta-peptide polymerization studied using fluorescence correlation spectroscopy.
BACKGROUND: The accumulation of fibrillar deposits of amyloid beta-peptide (Abeta) in brain parenchyma and cerebromeningeal blood vessels is a key step in the pathogenesis of Alzheimer's disease. In this report, polymerization of Abeta was studied using fluorescence correlation spectroscopy (FCS), a technique capable of detecting small molecules and large aggregates simultaneously in solution. RESULTS: The polymerization of Abeta dissolved in Tris-buffered saline, pH 7.4, occurred above a critical concentration of 50 microM and proceeded from monomers/dimers into two discrete populations of large aggregates, without any detectable amount of oligomers. The aggregation showed very high cooperativity and reached a maximum after 40 min, followed by an increase in the amount of monomers/dimers and a decrease in the size of the large aggregates. Electron micrographs of samples prepared at the time for maximum aggregation showed a mixture of an amorphous network and short diffuse fibrils, whereas only mature amyloid fibrils were detected after one day of incubation. The aggregation was reduced when Abeta was incubated in the presence of Abeta ligands, oligopeptides previously shown to inhibit fibril formation, and aggregates were partly dissociated after the addition of the ligands. CONCLUSIONS: The polymerization of Abeta is a highly cooperative process in which the formation of very large aggregates precedes the formation of fibrils. The entire process can be inhibited and, at least in early stages, partly reversed by Abeta ligands.
Alzheimer Disease↗
Presence of oxidized low density lipoprotein in nonrheumatic stenotic aortic valves.
The aim of the present study was to analyze if LDL particles trapped in stenotic aortic valve tissue undergo oxidative modification. Degenerative aortic stenosis affects >3% of the population >75 years of age in the Western world. Recent studies have revealed the presence of a chronic inflammatory process similar to what has been described in other degenerative diseases such as atherosclerosis. However, the underlying disease mechanisms of degenerative aortic stenosis still remain largely unknown. Six tricuspid stenotic valves, obtained at valve replacement, were compared with 3 control valves collected from hearts taken out during transplantation. The stenotic valves and the control valves were examined by immunohistochemistry, using antibodies against apoB, 4-hydroxynonenal-modified LDL, leukocytes, and HLA-DR. All valves were also stained with oil red O for neutral lipids. Extracellular neutral lipids were found in all stenotic valves, extending from the bases along the fibrosa layer. This lipid colocalized with apoB- and 4-hydroxynonenal-modified LDL immunoreactivity. 4-Hydroxynonenal-modified LDLs were present around calcium deposits, subendothelially, and in the deeper layer of the fibrosa. There was also a colocalization with macrophages, T lymphocytes, and HLA-DR expression. Control valves had a thin area of neutral lipid accumulation, a small amount of apoB, but no signs of inflammation. A distinct colocalization between oxidized LDLs, T-lymphocyte accumulation, and calcium deposits suggests that oxidized lipids may play a role in the disease process.
Adult↗
Antisense oligonucleotides to stromelysin mRNA inhibit injury-induced proliferation of arterial smooth muscle cells.
Smooth muscle cell migration and proliferation are important events in the formation of intimal lesions associated with atherosclerosis and restenosis following balloon angioplasty. To make this possible, the smooth muscle cell has to change from a contractile to an activated repair cell with capacity to synthesize DNA and extracellular matrix components. There is now considerable evidence that the extracellular matrix has important functions in modulating the phenotypic properties of smooth muscle cells, but less is known about the role of the matrix metalloproteinases. The present study investigates the role of stromelysin in the modulation of rat aortic smooth muscle cell morphology and function following mechanical injury in vitro and in vivo. Antisense mRNA oligonucleotides were used to investigate the role of stromelysin expression in injury-induced phenotypic modulation and the subsequent migration and proliferation of vascular smooth muscle cells. Cultured rat aortic smooth muscle cells and balloon-injured rat carotid arteries were used as experimental models. Light- and electron microscopy were used to follow changes in smooth muscle cell phenotype and lesion formation and incorporation of 3H-thymidine to detect DNA synthesis. Injury-induced DNA synthesis and migration in vitro were inhibited by 72% and 36%, respectively, by adding stromelysin antisense oligonucleotides to the medium prior to injury. In primary cultures, 67% of the smooth muscle cells treated with stromelysin antisense were retained in a contractile phenotype as judged by analysis of cell fine structure, compared to 15% untreated cells and 40% in cells treated with mismatched oligonucleotides. Examination of the carotid arteries one week after balloon injury likewise demonstrated a larger fraction of contractile cells in the inner parts of the media in vessels treated with antisense oligonucleotides compared to those treated with mismatched oligonucleotides. The neointima was also distinctly thinner in antisense-treated than in mismatched-treated and control arteries at this time. These findings indicate that stromelysin mRNA antisense oligonucleotides inhibited phenotypic modulation of rat arterial smooth muscle cells and so caused a decrease in migration and proliferation and neointima formation in response to vessel wall injury.
Animals↗
Effects of proteasome and calpain inhibitors on the structural reorganization and proliferation of vascular smooth muscle cells in primary culture.
Vascular smooth muscle cells exhibit a striking plasticity and are able to change from a differentiated, contractile phenotype to a more immature, synthetic phenotype. This includes a prominent structural reorganization with loss of myofilaments and construction of a large secretory apparatus. As a result, the cells lose their contractility and become able to migrate, proliferate, and secrete extracellular matrix components. In vivo, this phenotypic shift is a chief factor behind the involvement of smooth muscle cells in formation of atherosclerotic and restenotic lesions. Here, the effects of the proteasome inhibitors carbobenzoxy-leucyl-leucyl-leucinal, N-acetyl-leucyl-leucyl-norleucinal, and lactacystin on the morphologic structure and growth of rat aortic smooth muscle cells in primary culture were examined. Electron microscopic analysis revealed that the volume density of myofilaments was higher and the volume density of the endoplasmic reticulum and the Golgi complex was lower in cells exposed to these drugs than in solvent-treated controls. Moreover, diffuse material representing incompletely degraded proteins gathered in the cytoplasm of exposed cells. Similar material was also found in lysosomes. Immunogold staining showed a positive reaction in the diffuse cytoplasmic aggregates with antibodies against ubiquitin-protein conjugates and proteasomes, whereas the material collecting in lysosomes reacted only with those against ubiquitin-protein conjugates. Moreover, weak staining for smooth muscle alpha-actin was noted in the cytoplasmic aggregates. Otherwise, reactivity for this protein was concentrated in myofilaments. In addition to the effects on cell structure described above, the proteasome inhibitors blocked cell multiplication. This was probably due to a decreased rate of transition into a synthetic state as well as direct interference with cell cycle progression in synthetic cells. These observations suggest that proteasomes have the major responsibility for protein degradation during transition of smooth muscle cells from a contractile to a synthetic phenotype. If proteasome activity is inhibited, undegraded material accumulates in the cytoplasm and is only partially taken up into lysosomes for digestion. These findings raise the possibility that proteasome inhibitors may have a beneficial effect on vascular pathologies associated with phenotypic modulation and proliferation of smooth muscle cells.
Actins↗
Regulation of cell morphology in B lymphocytes by IL-4: evidence for induced cytoskeletal changes.
Lymphocyte activation is often accompanied by changes in cell morphology, for example, in cell adhesion or motility. IL-4 is a cytokine exerting many effects on B lymphocytes. In this study, we show that stimulation with LPS in combination with IL-4, but not LPS or IL-4 alone, results in a pronounced dendritic morphology of B cells. Using a culture system in which Abs directed to B cell surface markers are immobilized on the tissue culture plastic, we find that cell spreading can be mediated by a variety of Abs, including anti-CD44, -CD23, -LFA-1, -VLA-4, -ICAM-1, and -Ig. B cells stimulated with anti-Ig Abs plus IL-4, or anti-CD40 Abs in the presence or absence of IL-4, are also induced to spread, while IL-2, IL-5, or IL-10 in combination with LPS or alone fail to induce this. Spreading correlates with induction of tight cell aggregation. It is sensitive to cytochalasin B, indicating a requirement for intact actin cytoskeleton. CD44 is selectively detected in the detergent-insoluble fraction of cell lysates prepared from LPS plus IL-4-stimulated B cell cultures after Ab cross-linking of CD44, suggesting a membrane protein-cytoskeleton interaction. Interestingly, electron microscopy studies reveal induction of microvilli-like structures on LPS plus IL-4-stimulated blasts, suggesting that IL-4 can influence cell morphology on an ultra-structural level. In summary, our data show that stimulation with LPS plus IL-4 or ligation of CD40 is capable of inducing dramatic morphologic changes in murine B cells, which correlates with in vitro induction of strong cell adhesion.
Animals↗
Partitioning of cytoplasmic organelles during mitosis with special reference to the Golgi complex.
During mitosis, not only the genetic material stored in the nucleus but also the constituents of the cytoplasm should be equally partitioned between the daughter cells. For this sake, the dividing cell goes through an extensive structural reorganization and transport along the endocytic and exocytic pathways is temporarily arrested. Early in prophase, the radiating array of cytoplasmic microtubules disassembles and the membrane systems of the secretory apparatus start to split up. In metaphase, the nuclear envelope fragments and the condensing chromosomes associate with the forming mitotic spindle. The cisternal and tubular elements of the endoplasmic reticulum and the Golgi complex break down into small vesicles, presumably as the result of an imbalance between vesicle budding and fusion. In anaphase, the two sets of chromosomes are pulled apart and a cleavage furrow forms halfway between the spindle poles. Since most organelles occur in multiple and widely dispersed copies at this stage, they will be evenly distributed between the daughter cells. During telophase and cytokinesis, the preceding fragmentation process is reversed. A nuclear envelope reappears around the chromosomes and cytoplasmic microtubules reassemble. The endoplasmic reticulum is rebuilt as a continuous system of flattened cisternae and tubules. Stacks of Golgi cisternae arise from small vesicles and are rearranged in an interconnected network. In parallel, the biosynthetic functions of the cell are normalized and intracellular membrane traffic is resumed.
Cell Compartmentation↗