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Mature Phenotype (mature + phenotype)
Selected AbstractsVascular smooth muscle cell phenotypic modulation in culture is associated with reorganisation of contractile and cytoskeletal proteinsCYTOSKELETON, Issue 3 2001Nathalie F. Worth Abstract Smooth muscle cells (SMC) exhibit a functional plasticity, modulating from the mature phenotype in which the primary function is contraction, to a less differentiated state with increased capacities for motility, protein synthesis, and proliferation. The present study determined, using Western analysis, double-label immunofluorescence and confocal microscopy, whether changes in phenotypic expression of rabbit aortic SMC in culture could be correlated with alterations in expression and distribution of structural proteins. "Contractile" state SMC (days 1 and 3 of primary culture) showed distinct sorting of proteins into subcellular domains, consistent with the theory that the SMC structural machinery is compartmentalised within the cell. Proteins specialised for contraction (,-SM actin, SM-MHC, and calponin) were highly expressed in these cells and concentrated in the upper central region of the cell. Vimentin was confined to the body of the cell, providing support for the contractile apparatus but not co-localising with it. In line with its role in cell attachment and motility, ,-NM actin was localised to the cell periphery and basal cortex. The dense body protein ,-actinin was concentrated at the cell periphery, possibly stabilising both contractile and motile apparatus. Vinculin-containing focal adhesions were well developed, indicating the cells' strong adhesion to substrate. In "synthetic" state SMC (passages 2,3 of culture), there was decreased expression of contractile and adhesion (vinculin) proteins with a concomitant increase in cytoskeletal proteins (,-non-muscle [NM] actin and vimentin). These quantitative changes in structural proteins were associated with dramatic changes in their distribution. The distinct compartmentalisation of structural proteins observed in "contractile" state SMC was no longer obvious, with proteins more evenly distributed throughout the cytoplasm to accommodate altered cell function. Thus, SMC phenotypic modulation involves not only quantitative changes in contractile and cytoskeletal proteins, but also reorganisation of these proteins. Since the cytoskeleton acts as a spatial regulator of intracellular signalling, reorganisation of the cytoskeleton may lead to realignment of signalling molecules, which, in turn, may mediate the changes in function associated with SMC phenotypic modulation. Cell Motil. Cytoskeleton 49:130,145, 2001. © 2001 Wiley-Liss, Inc. [source] The Shiga toxin B-subunit targets antigen in vivo to dendritic cells and elicits anti-tumor immunityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2006Benoit Vingert Abstract The non-toxic B-subunit of Shiga toxin (STxB) interacts with the glycolipid Gb3, which is preferentially expressed on dendritic cells (DC) and B cells. After administration of STxB chemically coupled to OVA (STxB-OVA) in mice, we showed that the immunodominant OVA257,264 peptide restricted by Kb molecules is specifically presented by CD11c+CD8,, DC, some of them displaying a mature phenotype. Using mice carrying a transgene encoding a diphtheria toxin receptor (DTR) under the control of the murine CD11c promoter, which allows inducible ablation of DC, we showed that DC are required for efficient priming of CTL after STxB-OVA vaccination. Immunization of mice with STxB-OVA induced OVA-specific CD8+ T cells detected ex vivo; these cells were long lasting, since they could be detected even 91,days after the last immunization and were composed of both central and memory T cells. Vaccination of mice with STxB-OVA and STxB coupled to E7, a protein derived from HPV16, inhibited tumor growth in prophylactic and therapeutic experiments. This effect was mainly mediated by CD8+ T cells. STxB therefore appears to be a powerful carrier directly targeting DC in vivo, resulting in a strong and durable CTL response associated with tumor protection. [source] Site-specific expression of CD11b and SIRP, (CD172a) on dendritic cells: implications for their migration patterns in the gut immune systemEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2005Diane Bimczok Abstract Dendritic cells (DC) in the intestinal tract play a major role in directing the mucosal immune system towards tolerance or immunity. We analyzed whether different mucosal DC subsets in pigs have specific functions, localizations, or migration patterns in vivo. Therefore, we collected physiologically migrating DC by pseudo-afferent cannulation of the intestinal duct in eight Göttingen minipigs. Lymph DC were phenotypically and functionally characterized and compared to DC found on histological sections of porcine small intestine and mesenteric lymph nodes (MLN). Four different DC subpopulations were detected. Lamina propria (LP) DC were mainly CD11b+ signal regulatory protein,, (SIRP,)+, DC in Peyer's patches were mainly CD11b,/SIRP,+ in subepithelial domes and CD11b,/SIRP,, in interfollicular regions, whereas MLN DC were largely CD11b+/SIRP,,. Of these four subsets, only the CD11b+/SIRP,+ DC and the CD11b+/SIRP,, DC were present in lymph. This suggests that DC migration to MLN largely originates from the LP. Lymph DC expressed high levels of MHC class,II and costimulatory molecules and had a low capacity for FITC-dextran uptake, indicating a mature phenotype. However, lymph DC did not induce PBMC proliferation in MLR, and migration was not significantly influenced by mucosal antigen application. [source] Simvastatin regulates oligodendroglial process dynamics and survivalGLIA, Issue 2 2007Veronique E. Miron Abstract Simvastatin, a lipophilic statin that crosses the blood-brain barrier, is being evaluated as a potential therapy for multiple sclerosis (MS) due to its anti-inflammatory properties. We assessed the effects of simvastatin on cultures of rat newborn and human fetal oligodendrocyte progenitor cells (OPCs) and human adult mature oligodendrocytes (OLGs) with respect to cellular events pertaining to myelin maintenance and repair. Short-term simvastatin treatment of OPCs (1 day) induced robust process extension, enhanced differentiation to a mature phenotype, and decreased spontaneous migration. These effects were reversed by isoprenoid products and mimicked with an inhibitor of Rho kinase (ROCK), the downstream effector of the isoprenylated protein RhoA GTPase. Prolonged treatment (2 days) caused process retraction that was rescued by cholesterol, and increased cell death (4 days) partially rescued by either cholesterol or isoprenoid co-treatment. In comparison, simvastatin treatment of human mature OLGs required a longer initial time course (2 days) to induce significant process outgrowth, mimicked by inhibiting ROCK. Prolonged treatment of mature OLGs was associated with process retraction (6 days) and increased cell death (8 days). Human-derived OPCs and mature OLGs demonstrated an increased sensitivity to simvastatin relative to the rodent cells, responding to nanomolar versus micromolar concentrations. Our findings indicate the importance of considering the short- and long-term effects of systemic immunomodulatory therapies on neural cells affected by the MS disease process. © 2006 Wiley-Liss, Inc. [source] Cord blood mesenchymal stem cells propel human dendritic cells to an intermediate maturation state and boost interleukin-12 production by mature dendritic cellsIMMUNOLOGY, Issue 4 2009Lieke C. J. Van Den Berk Summary Pathogen-derived entities force the tissue-resident dendritic cells (DCs) towards a mature state, followed by migration to the draining lymph node to present antigens to T cells. Bone marrow mesenchymal stem cells (MSCs) modulate the differentiation, maturation and function of DCs. In umbilical cord blood an immature MSC population was identified. Remarkably, these immature stem cells modulated DCs in a different way. Marker expression was unchanged during the differentiation of monocytes towards immature DCs (iDCs) when cocultured with cord blood MSC [unrestricted somatic stem cells (USSCs)]. The maturation to mature DCs (mDCs) was enhanced when DCs were co-cultured with USSC, as evidenced by the up-regulation of costimulatory molecules. Endocytosis of dextran by iDCs was hampered in the presence of USSCs, which is indicative for the maturation of iDCs. Despite this maturation, the migration of iDCs cocultured with USSCs appeared to be identical to iDCs cultured alone. However, USSCs increased the migration of mDCs towards CCL21 and boosted interleukin-12 production. So, USSCs mature iDCs, thereby redirecting the antigen-uptake phenotype towards a mature phenotype. Furthermore, DC maturation by lipopolysaccharide (LPS) or USSCs reflects two distinct pathways because migration was unaffected when iDCs were matured by coculture with USSCs, while it was strongly enhanced in the presence of LPS. DCs are able to discriminate the different MSC subtypes, resulting in diverse differentiation programmes. [source] Early life events and their consequences for later disease: A life history and evolutionary perspectiveAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 1 2007Peter D. Gluckman Biomedical science has little considered the relevance of life history theory and evolutionary and ecological developmental biology to clinical medicine. However, the observations that early life influences can alter later disease risk,the "developmental origins of health and disease" (DOHaD) paradigm,have led to a recognition that these perspectives can inform our understanding of human biology. We propose that the DOHaD phenomenon can be considered as a subset of the broader processes of developmental plasticity by which organisms adapt to their environment during their life course. Such adaptive processes allow genotypic variation to be preserved through transient environmental changes. Cues for plasticity operate particularly during early development; they may affect a single organ or system, but generally they induce integrated adjustments in the mature phenotype, a process underpinned by epigenetic mechanisms and influenced by prediction of the mature environment. In mammals, an adverse intrauterine environment results in an integrated suite of responses, suggesting the involvement of a few key regulatory genes, that resets the developmental trajectory in expectation of poor postnatal conditions. Mismatch between the anticipated and the actual mature environment exposes the organism to risk of adverse consequences,the greater the mismatch, the greater the risk. For humans, prediction is inaccurate for many individuals because of changes in the postnatal environment toward energy-dense nutrition and low energy expenditure, contributing to the epidemic of chronic noncommunicable disease. This view of human disease from the perspectives of life history biology and evolutionary theory offers new approaches to prevention, diagnosis and intervention. Am. J. Hum. Biol. 19:1,19, 2007. © 2006 Wiley-Liss, Inc. © 2006 Wiley-Liss, Inc. [source] | |||||||||||||