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At least 649 records · Page 36Linked to original sources
PubMed1990

Antigen processing and presentation in vivo: the microenvironment as a crucial factor.

Antigen processing and presentation in vitro is an increasingly well understood phenomenon. However, in vivo, a large number of variables conspire to obscure and confuse. In this article, Nico van Rooijen attempts to bring order to events that occur in the spleen after antigenic challenge: starting with the large body of reliable in vitro data he incorporates information on splenic anatomy, cell trafficking and the cellular microenvironment to arrive at a physiological model for antigen handling in vivo.

Animals↗
PubMed1989

Fine-tuning of MHC class II gene expression in defined microenvironments.

Strict control of major histocompatibility complex class II gene expression is essential for proper functioning of the immune system. Recent transgenic mouse studies have revealed an intricate fine-tuning of class II gene transcription in microenvironments such as the germinal centers and thymic cortex and medulla.

Animals↗
PubMed1993

Nonisotopic in situ hybridization of amyloid beta protein precursor in Alzheimer's disease: expression in neurofibrillary tangle bearing neurons and in the microenvironment surrounding senile plaques.

We have used nonisotopic in situ hybridization techniques with biotinylated junctional oligonucleotide probes to study expression of amyloid precursor protein (APP) 695 and 751 mRNA in the hippocampal formation of Alzheimer's disease. Both mRNAs are strongly expressed in neurons of the hippocampal formation, particularly in the dentate gyrus granule cells and the pyramidal neurons of CA3. The patterns of expression of neither APP695 nor APP751 mRNA correlate well with the stereotyped topography of neurofibrillary tangles or senile plaques, which occur primarily in CA1 and subiculum. We double-labeled in situ sections with immunohistochemical reagents for neurofibrillary tangles or senile plaques. Neurons that contain neurofibrillary tangles continue to express APP mRNA. The level of APP695 and APP751 was measured semiquantitatively by optical density measurements in neurons that were close to (within 25 microns) or father from a senile plaque (more than 100 microns). There was no increase in expression in neurons in the immediate microenvironment of senile plaques. Our results suggest that no major change in distribution or type of APP mRNA accompanies neurofibrillary tangle or senile plaque development.

Adult↗
PubMed1986

Are some major in vivo effects of gold related to microenvironments of decreased selenium?

Gold interacts with selenium in vivo, and the normal distribution of selenium among tissues and subcellular compartments changes. Literature evidence shows that many of the effects of gold compounds on the polymorphonuclear neutrophil, macrophage, and lymphocyte cellular components of the immune system are similar to effects observed in these cellular components in selenium-deficient animals. Affected by these two metals are immune functions related to phagocytic cell migration, phagocytosis, microbial killing, lymphocyte mitogenesis/DNA synthesis, arachidonic acid metabolism/prostaglandin synthesis, and immunoglobulin production. The interaction of gold with selenium in vivo may be responsible for some of the multiparameter-based actions of gold compounds used in the treatment of inflammatory diseases such as rheumatoid arthritis. One mechanism by which gold exerts its clinical effects may be related to its interaction with selenium to produce, in specific microenvironments, decreased levels of this essential trace element.

Animals↗
PubMed1994

The influence of microenvironment on the cytotoxicity of TNF [symbol: see text] vitro.

PURPOSE: Investigations were undertaken to study the influence of oxygen levels on tumor necrosis factor [symbol: see text] (TNF [symbol: see text] toxicity in vitro. METHODS AND MATERIALS: The cell line used to assess the cytotoxicity of TNF [symbol: see text] the mouse fibroblast line L929. The cell line was incubated under conditions of 21%, 10%, 5% and 2% oxygen either before or during exposure to TNF [symbol: see text]. All incubations with TNF were for 24 h in the presence of 1 microgram/ml actinomycin D. Cell number was assessed immediately following treatment by a colormetric method. RESULTS: By preincubating L929 cells under various oxygen conditions for 24 h prior to incubating with TNF [symbol: see text], we show that pretreatment does influence TNF [symbol: see text] cytotoxicity since up to 50 times more TNF [symbol: see text] is required to elicit the same survival level when L929 cells have been preincubated for 24 h at oxygen levels relevant to those in solid tumors, that is 2% rather than at 21%. A 24 h preincubation under an environment of 5% oxygen is not as effective at inducing resistance to TNF [symbol: see text] as incubation under 2% oxygen. However, this resistance could be significantly enhanced by lengthening the preincubation time. Indeed cells cultured for five passages under 5% oxygen levels are approximately 50 times more resistant to TNF [symbol: see text] than cells cultured under 21% oxygen. The resistance induced by conditions of reduced oxygen tension could be reversed over a 24 h period if cells were returned to an environment containing of reduced oxygen tension could be reversed over a 24 h period if cells were returned to an environment containing 21% oxygen. CONCLUSION: The oxygen content of the cellular microenvironment has a profound influence on the cytotoxic action of TNF.

Animals↗
PubMed1991

Selective abnormalities in the thymic microenvironment associated with avian scleroderma, an inherited fibrotic disease of L200 chickens.

As a prelude to deciphering the mechanisms of intrathymic T-cell maturation we produced a panel of 18 monoclonal antibodies (mAbs) against chicken thymic stromal elements. Eleven of these detected epithelial cells. They were: pan-epithelial; subcapsule and peri-vascular (pan type 1 epithelium); subcapsular, perivascular and medulla; medulla; or cortex. Of particular interest were the sub-specificities within these regions, especially the subcapsular region. Four mAbs stained both epithelial and non-epithelial cells in discrete regions. In addition, three mAbs recognized only non-epithelial cells. One identified macrophages scattered throughout the thymus, another the connective tissue and another the medullary vascular endothelium. These reagents have provided an extensive profile of the thymic stromal architecture and revealed that these cells are equally as complex as the T cells whose differentiation they induce and regulate. While the mAbs provide a valuable means for studying the mechanisms of normal thymopoiesis, their clinical significance is unknown. UCD line 200 chickens develop an autoimmune disease manifest by dermal and internal organ fibrosis, T cell infiltrates of skin and other affected organs and production of multiple autoantibodies. We have used our panel of mAbs to evaluate the thymic microenvironment in these autoimmunity-prone chickens. A comparative analysis with control chickens revealed striking deficiencies in the L200 subcapsular regions coupled with excessive expression of MHC class II antigens, particularly in the cortex. We hypothesize that these abnormalities induce altered T-cell differentiation, thereby predisposing the L200 chickens to autoimmune disease.

Animals↗
PubMed1993

Immune privilege as the result of local tissue barriers and immunosuppressive microenvironments.

As the cellular and molecular bases of immune privilege are elucidated experimentally, the phenomenon emerges as an active and dynamic exercise in immune regulation. Local tissue factors play a key role in the establishment and maintenance of privilege, particularly tissue cytokines and mediators within the local microenvironment, which modify both the induction and expression of immunity to antigens that are introduced into, or arise within, privileged sites.

Animals↗
PubMed1994

B-lineage differentiation in normal and transformed cells and the microenvironment that supports it.

B-cell differentiation is a complex process mediated through interactions with the microenvironment of the bone marrow and fetal liver. These interactions alter patterns of gene expression and allow precursors to develop into Ig+ B cells. Recent work has shown that some of these events can be triggered in B-cell precursors transformed by Abelson virus. Other advances have refined our understanding of the role of cytokines, hormones and stromal cells in the differentiation process.

Abelson murine leukemia virus↗
PubMed2005

The extracellular microenvironment plays a key role in regulating the redox status of cell surface proteins in HIV-infected subjects.

There is an overwhelming interest in the study of the redox status of the cell surface affecting redox signaling in the cells and also predicting the total redox status of the cells. Measuring the total surface thiols (cell surface molecule thiols, csm-SH) we have shown that the overall level of surface thiols is tightly controlled. In vitro, the total concentration of intracellular glutathione (iGSH) seems to play a regulatory role in determination of the amounts of reduced proteins on cells. In addition, short term exposure of the cell surface to glutathione disulfide (GSSG, oxidized GSH) seems to reduce the overall levels of csm-SH suggesting that the function of some cysteine containing proteins on the cell surface may be regulated by the amount of GSSG secreted from the cells or the GSSG available in the extracellular environment. Examination of peripheral blood mononuclear cells (PBMCs) from healthy or HIV-infected subjects failed to reveal a similar correlation between the intra- and extracellular thiol status of cells. Although there is a relatively wide variation between individuals in both csm-SH and iGSH there is no correlation between the iGSH and csm-SH levels measured for healthy and HIV-infected individuals. There are many reports suggesting different redox active proteins on the cell surface to be the key players in the total cell surface redox regulation. However, we suggest that the redox status of the cells is regulated through a complex and tightly regulated mechanism that needs further investigation. In the mean time, overall surface thiol measurements together with case specific protein determinations may offer the most informative approach. In this review, we discuss our own results as well as results from other laboratories to argue that the overall levels of surface thiols on the exofacial membrane are regulated primarily by redox status of the cell surface microenvironment.

Cell Membrane↗
PubMed2005

PEG-based hydrogels as an in vitro encapsulation platform for testing controlled beta-cell microenvironments.

An in vitro encapsulation platform for systematically testing the effects of microenvironmental parameters on encapsulated islets was developed. The base encapsulation matrix was a biocompatible hydrogel formed via the photoinitiated polymerization of dimethacrylated poly(ethylene glycol) (PEGDM). The resulting inert encapsulation matrix affords control over the biochemical and biophysical cellular microenvironment and the introduction of systematic changes to this environment. The compatibility of the PEG-based encapsulation platform with pancreatic beta-cells was first established using a murine beta-cell line, MIN6. When cell-cell contacts were introduced via aggregation of MIN6 beta-cells prior to encapsulation, MIN6 beta-cells remained viable within the PEG hydrogel platform throughout 3weeks of in vitro culture. Proliferating cells were observed within encapsulated MIN6 aggregates qualitatively with bromodeoxyuridine staining and quantitatively by measuring the DNA content of encapsulation samples with time. MIN6 beta-cells were encapsulated in hydrogels formed from three PEGDM macromers of varying molecular weights (M (n)=4,000, 8,000, 10,000g/mol), and the resulting differences in hydrogel crosslinking density, which influences transport properties, did not affect encapsulated beta-cell survival. Encapsulated MIN6 beta-cells transplanted into diabetic mice returned blood glucose levels to normal levels, indicating in vivo function. Finally, the compatibility of the PEG encapsulation system with freshly isolated islets was confirmed.

Animals↗
PubMed2005

Crosstalk between cancer cells and bone microenvironment in bone metastasis.

Bone, as well as lung and liver, is one of the most preferential metastatic target sites for cancers including breast, prostate, and lung cancers. Although the precise molecular mechanisms underlying this preference need to be elucidated, it appears that bone microenvironments possess unique biological features that enable circulating cancer cells to home, survive and proliferate, and destroy bone. In conjunction, cancers that develop bone metastases likely have the capacity to utilize these unique bone environments for colonization and bone destruction. This crosstalk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. Disruption of this interaction will allow us to design mechanism-based effective and specific therapeutic interventions for bone metastases.

Animals↗
PubMed2005

Spatial microenvironment defines Ca2+ entry and Ca2+ release in salivary gland cells.

The difference of Ca(2+) mobilization induced by muscarinic receptor activation between parotid acinar and duct cells was examined. Oxotremorine, a muscarinic-cholinergic agonist, induced intracellular Ca(2+) release and extracellular Ca(2+) entry through store-operated Ca(2+) entry (SOC) and non-SOC channels in acinar cells, but it activated only Ca(2+) entry from non-SOC channels in duct cells. RT-PCR experiments showed that both types of cells expressed the same muscarinic receptor, M3. Given that ATP activated the intracellular Ca(2+) stores, the machinery for intracellular Ca(2+) release was intact in the duct cells. By immunocytochemical experiments, IP(3)R2 colocalized with M3 receptors in the plasma membrane area of acinar cells; in duct cells, IP(3)R2 resided in the region on the opposite side of the M3 receptors. On the other hand, purinergic P2Y2 receptors were found in the apical area of duct cells where they colocalized with IP(3)R2. These results suggest that the expression of the IP(3)Rs near G-protein-coupled receptors is necessary for the activation of intracellular Ca(2+) stores. Therefore, the microenvironment probably affects intracellular Ca(2+) release and Ca(2+) entry.

Adenosine Triphosphate↗
PubMed2006

Conformation and microenvironment of the active site of a low molecular weight 1,4-beta-D-glucan glucanohydrolase from an alkalothermophilic Thermomonospora sp.: involvement of lysine and cysteine residues.

Conformation and microenvironment at the active site of 1,4-beta-D-glucan glucanohydrolase was probed with fluorescent chemo-affinity labeling using o-phthalaldehyde. OPTA has been known to form a fluorescent isoindole derivative by cross-linking the proximal thiol and amino groups of cysteine and lysine. Modification of lysine of the enzyme by TNBS and of cysteine residue by PHMB abolished the ability of the enzyme to form an isoindole derivative with OPTA. Kinetic analysis of the TNBS and PHMB-modified enzyme suggested the presence of essential lysine and cysteine residues, respectively, at the active site of the enzyme. The substrate protection of the enzyme with carboxymethylcellulose (CMC) confirmed the involvement of lysine and cysteine residues in the active site of the enzyme. Multiple sequence alignment of peptides obtained by tryptic digestion of the enzyme showed cysteine is one of the conserved amino acids corroborating the chemical modification studies.

Actinomycetales↗
PubMed2003

1H NMR studies of the effect of mutation at Valine45 on heme microenvironment of cytochrome b5.

1D and 2D (1)H NMR were employed to probe the effects on the heme microenvironment of cytochrome b(5) caused by the mutation from Val45 to Tyr45, His45 and Glu45. Compared with wild type (WT) cytochrome b(5), in all mutants the heme ring are CCW rotated relative to the imidazole planes of axial ligands and the angles beta between two axial ligand imidazole planes are not changed, being in agreement with the temperature dependence of the shifts of the heme protons. The ratios of heme isomers (major to minor) are smaller than that in WT. The 4-vinyl group of the heme in V45Y assumes cis-orientation, being similar to that of WT, while in V45E and V45H, both cis and trans orientation are found. The relationships between the structure and biological function of the mutants are discussed in terms of the geometry of heme and axial ligands, the hydrophobicity of heme pocket and the electrostatic potential of the heme-exposed area.

Animals↗
PubMed2005

Tuning the sol-gel microenvironment for acetylcholinesterase encapsulation.

The effect of the sol-gel microenvironment on the activity of acetylcholinesterase, an enzyme of high bio-analytical interest, is presented and is correlated to the overall analytical performance of corresponding biosensors. The sol-gel membranes are initially optimized with respect to the catalyst and the TEOS:H2O ratio (r), for mechanical stability, porosity, and hydrophobicity as well as in terms of enzymatic activity. FT-IR and electrochemical impedance spectroscopy (EIS) are used to probe the configuration and rotational mobility of the enzyme within the sol-gel matrices. Overall, it is observed that the rotational mobility of the protein can be correlated with the sensitivity of the biosensor. Optimum biosensor performance is obtained for base-catalyzed sol-gels with r values close to 2. The biosensor has sensitivity of 2.5 microA/mm, a linear range of response between 1 and 3mm, response time of about 30s, and sensor-to-sensor reproducibility (RSD) of 3%. These analytical characteristics are far superior to previously reported sol-gel biosensors.

Acetylcholinesterase↗
PubMed2006

Fabrication methods of an engineered microenvironment for analysis of cell-biomaterial interactions.

Success in tissue engineering requires an understanding of how cells integrate the signals presented from the microenvironment created by biomaterial scaffolds to alter their responses. Besides the presence of chemical stimuli, there is growing evidence that the spatial organization of cells and tissue within a 3-dimensional (3-D) extracellular matrix (ECM) context is a critical element in controlling cellular function. Therefore, in order to direct cells toward a desirable tissue structure, it is necessary to engineer biomaterials to have spatiotemporal control of the presentation of regulatory signals. Given that, micro-patterning techniques have profited by combining micro-fabrication technology with the chemical conjugation of biologically active molecules to provide new culture systems where cells can be cultured within a specific geometry. The micro-engineered environments have been developed as 2- and 3-D structures, which have proven greatly useful as versatile platforms to study cell, biomaterial, and ECM interactions on both macroscopic and microscopic levels. The main focus of this review is a brief summary of the use of micro-engineered substrates in the analysis of cell-biomaterial interactions with the aim to provide an introductory overview of practical applications available in the literature. In particular, topics regarding (1) the soft-lithography technique to prepare micro-patterned substrates for the spatial control of cell adhesion, (2) biomaterials stiffness-dependent cellular responses, and (3) the microarray techniques for analysis of cell/biomaterials interactions are discussed.

Animals↗
PubMed2006

Targeting the stromal microenvironment in chronic inflammation.

A characteristic feature of chronic inflammatory reactions is their persistence and predilection for certain sites. The molecular basis for such tissue tropism (as, for example, seen with metastatic spread) has until recently remained obscure, but recent studies have strongly implicated tissue-resident, stromal cells, such as macrophages, endothelial cells and fibroblasts. These cell types make attractive therapeutic targets as they help define the three-dimensional structure of tissues and are key orchestrators of the inflammatory infiltrate. Most current anti-inflammatory therapies target immune cells in an attempt to inhibit the production of pro-inflammatory mediators; however, an equally important target is the active induction of anti-inflammatory mediators involved in the resolution of inflammation. Recent work suggests that stromal cells are an important source of these mediators. Targeting of multiple signals may be required to inhibit tissue damage associated with inflammatory disease. Cells of the monocyte lineage are present as tissue-resident cells and interact closely with other stromal populations. These cells form an ideal target for modulation of the inflammatory environment as, in some cases, they appear to induce tissue repair. Therapeutic manipulation of the stromal microenvironment has been particularly effective in treating cancer and is likely to provide a novel method to achieve improved control of chronic inflammatory disease.

Angiogenic Proteins↗
PubMed2005

Metastases and their microenvironments: linking pathogenesis and therapy.

The pathogenesis of metastasis depends on multiple favorable interactions of tumor cells with host homeostatic mechanisms. Interruption of one or more of these interactions can lead to the inhibition or eradication of cancer metastases. For many years, all efforts to treat cancer concentrated on the inhibition of growth or the destruction of tumor cells. A strategy of both eradication of tumor cells (e.g. by chemotherapy and immunotherapy) and modulation of the host microenvironment (e.g. tumor vasculature and hypoxia) is an additional, relatively novel approach to cancer treatment. Recent advances in our understanding of the biological basis of cancer metastasis open up unprecedented opportunities for translating basic research to clinical treatment of cancer. This research includes the unraveling of the genetic make-up of tumors and genome-wide expression analyses, thereby identifying many potential targets for therapy. Drugs acting on tumor cells which have a metastasis-prone mutational or expression status (by classical or targeted chemotherapy) as well as drugs affecting host-mediated survival pathways must be combined in order to create therapeutic synergy. Therapeutic maneuvers may target receptor tyrosine kinases (EGFR, VEGFR, FGFR), chemokines or G-protein-coupled receptors (CXCR4, CXCR2, EphB2), hypoxia-inducible factor (HIF), and signaling pathways (c-Src, PI3K, Akt, chaperon complexes) in tumor cells. Moreover, stromal and immunological cells and their cytokines coordinate critical pathways that exert important roles in the ability of tumors to invade and metastasize, thus suppressive cytokines (IL-6 and IL-10) and neutralizing specific antibodies might subvert conditions for metastasis.

Animals↗