Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cellular Microenvironment”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources
PubMed1977

[Stimulation of hematopoietic stem cells by antilymphocyte serum].

The physiopathogeny of aplastic anemia is still unknown, it can be related to a stem cell defect or a microenvironment disease. An autoimmune origin is suspected but not as yet proved. To demonstrate the autoimmune origin of some cases of aplastic anemia, we have studied the effect of antilymphocyte globulin (ALG) on the hematopoiesis of aplastic patients by serial hematological and bone marrow investigation including blood counts, bone marrow cellularity, scanning with indium and technetium and granulocytic colonies in agar, 8 out of 17 patients had a response to ALG as shown by a rise of granulocytes and reticulocytes counts, increase of bone marrow cellularity and number of granulocytic colonies. This study tends to show that ALG has a stimulating effect on hematopoiesis in some cases of severe aplastic anemia.

Anemia, Aplastic↗
PubMed2006

Characterization of nascent HDL particles and microparticles formed by ABCA1-mediated efflux of cellular lipids to apoA-I.

The nascent HDL created by ABCA1-mediated efflux of cellular phospholipid (PL) and free (unesterified) cholesterol (FC) to apolipoprotein A-I (apoA-I) has not been defined. To address this issue, we characterized the lipid particles released when J774 mouse macrophages and human skin fibroblasts in which ABCA1 is activated are incubated with human apoA-I. In both cases, three types of nascent HDL containing two, three, or four molecules of apoA-I per particle are formed. With J774 cells, the predominant species have hydrodynamic diameters of approximately 9 and 12 nm. These discoidal HDL particles have different FC contents and PL compositions, and the presence of acidic PL causes them to exhibit alpha-electrophoretic mobility. These results are consistent with ABCA1 located in more than one membrane microenvironment being responsible for the production of the heterogeneous HDL. Activation of ABCA1 also leads to the release of apoA-I-free plasma membrane vesicles (microparticles). These larger, spherical particles released from J774 cells have the same PL composition as the 12 nm HDL and contain CD14 and ganglioside, consistent with their origin being plasma membrane raft domains. The various HDL particles and microparticles are created concurrently, and there is no precursor-product relationship between them. Importantly, a large fraction of the cellular FC effluxed from these cells by ABCA1 is located in microparticles. Collectively, these results show that the products of the apoA-I/ABCA1 interaction include discoidal HDL particles containing different numbers of apoA-I molecules. The cellular PLs and cholesterol incorporated into these nascent HDL particles originate from different cell membrane domains.

ATP Binding Cassette Transporter 1↗
PubMed2004

CRBP-III:lacZ expression pattern reveals a novel heterogeneity of vascular endothelial cells.

Vascular endothelial cells are structurally and functionally heterogeneous. However, the molecular basis of this heterogeneity remains poorly defined. We used subtractive and differential screening to identify genes that exhibit heterogeneous expression patterns among vascular endothelial cells. One such gene is cellular retinol binding protein III (CRBP-III/Rbp7). Analysis of the lacZ knockin line for this gene (CRBP-III:lacZ) revealed a novel organ-specific vascular endothelial expression pattern. LacZ was expressed in vascular endothelial cells in heart, skeletal muscle, adipose tissues, thymus, and salivary gland. However, it was not detected in other tissues such as brain, liver, and lung. Furthermore, the expression within each organ was primarily restricted to small capillary endothelial cells, but could not be detected in larger vessels. This organ-specific vascular endothelial expression of CRPB:lacZ is relatively resistant to the changes of organ microenvironment. However, the level of expression can be modified by vitamin A deficiency. Therefore, our results provide novel molecular evidence for the heterogeneity of vascular endothelial cells.

Animals↗
PubMed2003

Role of cancer cell-stroma interaction in invasive growth of cancer cells.

Invasive growth is one of the hallmarks of cancer malignancy. To date, a significant body of evidence is accumulating in favor of the notion that invasive growth results from the cross-talk between cancer cells and the host stromal cells, comprising fibroblasts (myofibroblasts), endothelial cells, and leukocytes, all of which are themselves invasive. In this review we describe cross-talk between invasive cancer cells and host stromal fibroblasts and an impact of pericellular microenvironment on the invasive phenotype of cancer cells, focusing on two molecules, extracellular matrix metalloproteinase inducer (EMMPRIN, also known as tumor cell-derived collagenase stimulatory factor, basigin, CD147) and hepatocyte growth factor (HGF, also known as scatter factor). Both molecules are deeply involved in the regulation of invasion-associated cellular activities, such as pericellular proteolysis, migration and ectopic survival of cancer cells.

Antigens, CD↗
PubMed2007

Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells.

The systemic administration of keratinocyte growth factor (KGF) enhances T-cell lymphopoiesis in normal mice and mice that received a bone marrow transplant. KGF exerts protection to thymic stromal cells from cytoablative conditioning and graft-versus-host disease-induced injury. However, little is known regarding KGF's molecular and cellular mechanisms of action on thymic stromal cells. Here, we report that KGF induces in vivo a transient expansion of both mature and immature thymic epithelial cells (TECs) and promotes the differentiation of the latter type of cells. The increased TEC numbers return within 2 weeks to normal values and the microenvironment displays a normal architectural organization. Stromal changes initiate an expansion of immature thymocytes and permit regular T-cell development at an increased rate and for an extended period of time. KGF signaling in TECs activates both the p53 and NF-kappaB pathways and results in the transcription of several target genes necessary for TEC function and T-cell development, including bone morphogenetic protein 2 (BMP2), BMP4, Wnt5b, and Wnt10b. Signaling via the canonical BMP pathway is critical for the KGF effects. Taken together, these data provide new insights into the mechanism(s) of action of exogenous KGF on TEC function and thymopoiesis.

Animals↗
PubMed2006

The role of HIF-1alpha in maintaining cartilage homeostasis and during the pathogenesis of osteoarthritis.

As a consequence of the avascular nature of cartilage the microenvironment in which chondrocytes must exist is characterized by hostile conditions, most prominently very low levels of oxygen (hypoxia). In recent years, a vast number of papers reporting on the role of hypoxia in cartilage development and disease has been published. It is well established today that the principal mediator of cellular adaptation to hypoxia, the transcription factor hypoxia inducible factor (HIF)-1, is of pivotal importance for survival and growth arrest of chondrocytes during cartilage development as well as energy generation and matrix synthesis of chondrocytes in healthy as well as osteoarthritic cartilage. With this commentary we aim to briefly discuss the recently published literature in this field.

Cartilage, Articular↗
PubMed1997

Chemical analysis of single cells and exocytosis.

Recent advances in the development of microscale analytical techniques have allowed minute amounts of compounds of biological interest to be monitored in microenvironments. Microcolumn separation techniques, such as microcolumn liquid chromatography and capillary electrophoresis, provide a means of obtaining high-efficiency separations of analytes in picoliter to femtoliter volume samples. Voltammetric microelectrode techniques, such as amperometry and fast-scan cyclic voltammetry, are ideally suited for monitoring transiently occurring chemical events in cellular and subcellular processes owing to their rapid response times and small structural dimensions. The principles and applications of these techniques in single-cell analysis are discussed throughout this review. Multicomponent separations and quantitations of large invertebrate neurons of the land snail Helix neurons and the pond snail Planorbis corneus dopamine neurons, and of small mammalian cells, bovine adrenal cells, rat PC12 cells, and human lymphocytes, by use of microcolumn liquid chromatography and capillary electrophoresis are presented. Electrochemical monitoring of neurotransmitter exocytosis from single adrenal cells, from PC12 cells, and from the cell body of the Planorbis dopamine neuron is highlighted. Results obtained from both separation and voltammetric techniques in single-cell analyses will provide a better understanding of cellular and/or neuronal chemistry and biology in complicated living environments.

Adrenal Medulla↗
PubMed2001

TGF-beta1 is elevated in breast cancer tissue and regulates nitric oxide production from a number of cellular sources during hypoxia re-oxygenation injury.

Cellular response to treatment is dependent on the metabolic preconditioning of individual cells, which is a reflection of environmental conditions. Within solid tumours there are areas of different oxygen tension, which, we hypothesise, may indicate that cells are exposed to conditions that change continually. Other characteristics of the solid-tumour microenvironment include the production of growth factors, one of which is transforming growth factor (TGF)-beta1. As part of this study, we measured TGF-beta1 and found it raised in the serum of breast cancer patients compared with controls (98.24+/-13.25 vs. 48.87+/-12.14 ng/mL; P < 0.05; n = 7), and in the conditioned medium of breast tumour explant tissue compared with matched normal tissue (21.1+/-5.3 vs. 4.7+/-1.2 ng TGF-beta1/gram of tissue; P < 0.05; n = 11). Nitric oxide (NO) is a cytotoxic molecule produced by a large number of cells and thought to have antimetastatic properties. In order to observe the effect of conditions within breast tumours on NO production, we exposed macrophages, endothelial cells and tumour cells to hypoxia re-oxygenation in vitro, both in the presence and absence of TGF-beta1. Hypoxia stimulated increased NO production in both macrophages (normoxia: 0.34+/-0.04 nmol/L nitrite vs. hypoxia: 1.04+/-0.18 nmol/L nitrite; P < 0.05) and endothelial cells (normoxia: 0.02+/-0.01 nmol/L nitrite vs. hypoxia: 0.21+/-0.07 nmol/L nitrite; P < 0.05). NO production in macrophages, endothelial cells and tumour cells was reduced significantly following hypoxia in the presence of TGF-beta1 in a concentration-dependent manner. These results suggest that, within breast tumours, tumour-derived TGF-beta1 in combination with environmental conditions may result in decreased local NO production, which could have implications for tumour growth.

Breast Neoplasms↗
PubMed1987

The use of congenital immunologic mutants to probe autoimmune disease in New Zealand mice.

To further our understanding of autoimmunity, many laboratories have concentrated on the study and manipulation of murine lupus in several strains. Although direct extrapolation of data from animal to man must proceed with caution, the use of such animal systems, both in vitro and in vivo, has been an enormous help in the development of immunologic concepts. Our laboratory has been studying murine lupus by selective breeding of specific genetic immune defects onto New Zealand mice. Specifically, we have used congenital immunologic mutations resulting in asplenia (Dh/+), athymia (nu/nu) and immunodeficiency (Xid) as a means of probing the natural history of immunopathology in one such murine model of autoimmunity New Zealand (NZ) mice. These studies have provided important insights into the ontogeny of autoimmunity. NZB.Xid mice have been particularly valuable and have become a useful tool for dissecting the B cell defects of NZ mice. The Xid gene is dominant over the premature polyclonal activation of NZB mice and acts almost exclusively on B cells that are involved in autoantibody production in NZB mice. Nonetheless, the fact that autoantibody production can occur in a small percent of very old NZB.Xid mice, which have the same phenotype as other NZB.Xid mice, suggests that it can be produced by a mechanism other than a generalized polyclonal expansion and is not dependent on the circulatory or splenic frequency of the Lyb 5 subset of cells. Finally, NZB.Xid mice are unable to produce autoantibodies even after maturing in an aged NZB microenvironment, which suggests that the cell population missing in NZB.Xid mice are important for autoantibody production.

Animals↗
PubMed1988

A contribution to the study of damage and regeneration of hemopoiesis during fractionated irradiation and repeated bone marrow transplantation.

The experiment was aimed at studying two contradictory actions: damage to hemopoietic organs during application of radiation doses per fraction and regenerative efforts of the organism supported by repeated bone marrow transplantation. The mice received doses of 3 Gy of 60Co-gamma rays total body irradiation at four-day intervals up to a total dose of 18 Gy. After each dose per fraction half of the animals were injected with 10(6) bone marrow cells. At four-day intervals evaluations were made of the blood count, bone marrow and spleen cellularities, and spleen mass. In animals subjected only to irradiation the damage to hemopoietic organs was becoming deeper until the end of observation. In bone marrow recipients the decrease in bone marrow cellularity and the number of leukocytes stopped after day 16, and there was a steep growth of splenic cellularity and mass; the decrease in erythrocyte count stopped on day 20. Obviously a certain recovery of hemopoiesis occurred after the total dose of 12 Gy between days 12 and 16. The lodging of injected hemopoietic stem cells and their proliferation had to be preceded by a regeneration of the hemopoietic microenvironment.

Animals↗
PubMed1994

Mucosal microenvironment and mucosal response.

Considerable investigative effort is currently being directed towards the use of oral immunization for the prevention of mucosal infections, including otitis media, in infancy and childhood. The development of immune response to mucosally introduced vaccines or environmental antigens is significantly influenced by the mucosal microflora, enzymatic activity, factors influencing epithelial permeability and the nature of vaccine antigens administered. Studies carried out during the past several years have suggested that antigen uptake, antigen processing, and immune response to environmental antigens in the respiratory and intestinal mucosa are greatly altered by coexisting mucosal infections. High levels of ovalbumin or ragweed antigens were often observed in the serum associated with increased IgE-specific antibody responses following concurrent infection with respiratory syncytial virus, or rotavirus, respectively. The influence of the mucosal enzymatic environment has been recently evaluated after oral immunization with replicating poliovaccine or parenteral immunization with inactivated poliovaccines. High levels of neutralizing and VP3-specific antibody response and antibody activity against antigenic determinants generated in the intestine were observed characteristically after oral immunization with replicating virus. Such responses were conspicuously absent after parenteral immunization. These observations suggest that diverse elements of the mucosal microenvironment play an important role in the outcome of infections and development of immune responses at mucosal surfaces.

Animals↗
PubMed1995

[Functional morphology of the spleen].

The spleen was till the first half of the twentieth century considered to represent an organ of no special significance. Nowadays its clearance function and position in the immunity system is thoroughly investigated. Informations on its cellular composition and compartments are sufficient. The problems coinciding with circulation in the spleen are solved. The study of interactions of T and B lymphocytes regarding the development of humoral immunity do not provide clear results. Unclear remain also the relations of extracellular and cellular structures. The localisation of the spleen in blood circulation and large amount of migrating lymphocytes justify its significant position in the protection of host against infections spreading haematogenously. It is not inevitable for survival, but its removal increases the risk of unmanageable infections carried by bacteria with polysaccharide capsules. The microenvironment in the spleen enables intercellular relations and determines the development of immune reactions. Microcirculation enables it to function as a biological filter without the necessity of specialized filtrating structures being present. In consequence of blood filtration everything leaks into the extravasal space. Subsequently all components normally constituting the blood return back into the blood within vessels. That is why no special structures are formed in order to filter individual components from the blood. All components that should not be present in the blood are excluded extravasally. The substances which are not let through the wall of sinuses into the blood, remain in the marginal zone and in the red pulp. The macrophages of the marginal zone and red pulp destroy and degrade the unrequired substances. (Ref. 26).

Animals↗
PubMedDate not supplied

Cellular aspects of the pathogenesis of radiation--induced thymic lymphomas in C57 BL mice (review).

Radiation-induced thymic lymphomas in C57Bl/Ka mice are interesting models for studying the successive steps of carcinogenesis. Irradiation initiates "preleukemic" cells, which are promoted to become neoplastic. Studies in mice in which lymphoma development is inhibited by a bone marrow transplantation after irradiation suggest that radiation--induced alterations to the T cell lineage, and particularly to thymic microenvironment, are critical for the promotion of preleukemic cells. It is proposed that the lack of physiological differentiation signals within the thymus, as a result of irradiation, allows these cells to escape the normal controls of thymocyte production and pushes them towards neoplastic transformation. A disturbance in the production of cytokines may be involved, since exogenous cytokines, such as Interferon gamma or Tumor Necrosis Factor a, can inhibit radiation-induced lymphomagenesis, reproducing the effects of bone marrow transplantation. The model is thus suitable for studying the mechanisms of carcinogenesis and designing biological manipulation devoted to cancer prevention in individuals who have been exposed to oncogenic agents.

Animals↗
PubMed1988

Cholesterol transfer between lipid vesicles. Effect of phospholipids and gangliosides.

The effect of lipid composition on the rate of cholesterol movement between cellular membranes is investigated using lipid vesicles. The separation of donor and acceptor vesicles required for rate measurement is achieved by differential centrifugation so that the lipid effect can be quantified in the absence of a charged lipid generally used for ion-exchange-based separation. The rate of cholesterol transfer from small unilamellar vesicles (SUVs) containing 50 mol% cholesterol to a common large unilamellar vesicle (LUV) acceptor containing 20 mol% cholesterol decreases with increasing mol% of sphingomyelin in the SUVs, while phosphatidylethanolamine and phosphatidylserine have no appreciable effect at physiologically relevant levels. There is a large decrease in rate when phosphatidylethanolamine constitutes 50 mol% of donor phospholipids. Interestingly, gangliosides which have the same hydrocarbon moiety as sphingomyelin exert an opposite effect. The effect of spingomyelin seems to be mediated by its ability to decrease the fluidity of the lipid matrix, while that of gangliosides may arise from a weakening of phosphatidylcholine-cholesterol interactions or from a more favourable (less polar) microenvironment for the desorption of cholesterol provided by the head-group interactions involving sugar residues. If the effect of asymmetric transbilayer distribution of lipids is taken into consideration, the observed composition-dependent rate changes could partly account for the large difference in the rates of cholesterol desorption from the inner and outer layers of plasma membrane. Such rate differences may be responsible for an unequal steady-state distribution of cholesterol among various cellular membranes and lipoproteins.

Biological Transport↗
PubMed1985

Procoagulant activity of mouse and human cultured cells following various types of transformation.

The presence of fibrin deposits in the microenvironment of tumor cells has been reported repeatedly and considered to play an important role in tumor biology. Among the mechanisms by which fibrin may be deposited in tumors, procoagulant activities (PCA) of different types have been described in cancer cells. The present study was aimed at establishing whether the nature of cellular PCA was a characteristic associated with malignant transformation. PCA of normal and transformed cells was investigated on pairs of murine and human origin. The transformed counterparts were obtained after treatment with low-dose radiation, chemical carcinogen, viral infection or after in vitro spontaneous immortalization. Both before and after any type of transformation cell PCA was of the tissue thromboplastin type, identified on the basis of biological criteria: requirement of factor VII for its expression and lack of inhibition by the serine protease inhibitor diisopropylfluorophosphate (DFP). Transformed cells of murine origin showed significantly lower activity than their normal counterparts, whereas all the transformed human cell lines expressed significantly higher activity than normal. An inverse correlation between the levels of PCA and the cell density in culture was observed in all but one of the lines tested. These findings suggest that the factor X activating property described in some tumors or in transformed cells cannot be considered as a general marker of transformation.

Animals↗
PubMed1998

Estrogen enhances proliferative capacity of cardiac fibroblasts by estrogen receptor- and mitogen-activated protein kinase-dependent pathways.

The role of female hormones in the prevalence of cardiac diseases are recognized but not fully explored. Proliferation of cardiac fibroblasts, the cellular origin of the extracellular matrix proteins, growth factors and cytokines in the heart, is an important underlying mechanism in the pathophysiological remodeling of the myocardium. In this study, we have investigated the effect of estrogen (17 beta-estradiol) on proliferative capacity of cardiac fibroblasts obtained from adult female rat heart. DNA synthesis, as determined by incorporation of 3H-thymidine into DNA, increased in estrogen-treated cells. In the presence of tamoxifen, an anti-estrogen with high affinity for estrogen receptor. 17 beta-estradiol-induced stimulation of DNA synthesis was abolished. Alpha-estradiol, a stereo-isomer which does not bind the estrogen receptor, did not change DNA synthesis. In the presence of a synthetic inhibitor of MAP kinase pathway. PD98059, estrogen failed to stimulate DNA synthesis. In-gel kinase assays showed rapid and transient increased phosphorylation of MAP kinase substrate, myelin basic protein (MBP), at 42 and 44 kDa by 17 beta-estradiol, which was not observed in the presence of PD98059 and tamoxifen, not induced by alpha-estradiol and persisted in the absence of protein kinase C. In vitro kinase assay confirmed 17 beta-estradiol-induced activation of ERK1 and ERK2, with predominant effect on ERK2 in cardiac fibroblasts. The results of immunofluorescent light microscopy using anti-type alpha and beta estrogen receptor antibodies showed the expression of estrogen receptor types alpha and beta in control untreated cells, and indicated that type beta receptor is the predominant type with both cytoplasmic and nuclear localization. 17 beta-estradiol treatment of cardiac fibroblasts induced the translocation of receptor protein to the nuclei. Together, these data provide evidence that cardiac fibroblasts are cellular targets for direct effects of estrogen, and that this hormone enhances proliferative capacity of cardiac fibroblasts via estrogen receptor- and MAP kinase-dependent mechanisms. These data further suggest that estrogen, by its growth-enhancing effects in cardiac fibroblasts, can regulate the remodeling of the extracellular matrix and alter the microenvironment of cardiac cells, and hence exert an impact on the integrity of myocardial function.

Animals↗
PubMed1993

Adaptive immune responses during murine pregnancy: pregnancy-induced regulation of lymphokine production by activated T lymphocytes.

OBJECTIVE: We hypothesized that the lymphokine production by splenocytes and decidual lymphocytes would be altered because of changes in immunoregulation during pregnancy. STUDY DESIGN: Splenocytes and decidual lymphocytes were isolated from syngeneic and allogeneic pregnant mice at different times of gestation. The lymphocytes (10(7) cells/ml) were stimulated with anti-CD3 antibody, and culture supernatants were assayed for several lymphokines, including interleukin-2, interferon-gamma, interleukin-4, interleukin-6, granulocyte-macrophage colony-stimulating factor, and interleukin-3. Statistical analysis was by analysis of variance or paired t test. RESULTS: Activated splenocytes produced significantly less interleukin-2 and more interleukin-4, interleukin-6, and interleukin-3 as murine pregnancy advanced. Production of interferon-gamma and granulocyte macrophage colony-stimulating factor by activated splenocytes peaked in the first 8 to 14 days of pregnancy. Stimulated decidual lymphocytes produced modest amounts of interleukin-6, granulocyte-macrophage colony-stimulating factor, and interleukin-3 during pregnancy but no interleukin-2, interferon-gamma, or interleukin-4. Similar results were found for both syngeneic and allogeneic matings. CONCLUSIONS: Our findings indicate that splenocyte lymphokine production favors interleukin-4 production over interleukin-2 production. This finding suggests that antibody production would be enhanced and cytotoxic cellular immune responses inhibited during pregnancy. These changes occurred regardless of mating partner, suggesting that the specific antigenic stimulus during normal pregnancy does not regulate lymphokine production. Activated splenocytes and decidual lymphocytes were found to differ in their capacity to produce lymphokines, indicating that the decidua constitutes a distinct and unique immunologic microenvironment.

Animals↗
PubMed1986

The K.G. McKenzie award lecture--1986. Effects of extracellular matrix proteins on the growth and differentiation of an anaplastic glioma cell line.

Efforts to determine the factors responsible for reversing malignancy in the central nervous system may not only increase our understanding of the growth of primary human brain tumors, but may eventually prove to be of therapeutic benefit as well. We therefore devised a model system to study the effects of extracellular matrix (ECM) proteins on the malignant phenotype of an anaplastic glioma line, U-343 MG-A. Well-characterized cultures derived from normal human leptomeninges were grown to confluence and maintained for 2 weeks. The pia-arachnoid cells were then removed with detergent and base, leaving behind an ECM enriched in laminin, fibronectin, types I and IV collagen, and procollagen III. U-343 MG-A tumor cells planted on top of this normal ECM were profoundly growth inhibited, developed multiple slender cytoplasmic processes similar to those of normal astrocytes, and expressed more GFAP per cell than did tumor cells growing on plastic alone. The growth of U-343 MG-A tumor cells in flasks coated with purified fibronectin or laminin was not significantly inhibited. However, U-343 MG-A cultures grown in flasks coated with type I or IV collagen showed decreased cellular proliferation and altered cell morphology. Conditioned medium from U-343 MG-A tumor cells growing on plastic alone contained a 64 kD activated metalloprotease. U-343 MG-A tumor cells growing on the pia-arachnoid ECM do not demonstrate such proteolytic activity. We conclude that the tumor cell microenvironment is extremely important in modulating the growth and differentiation of an anaplastic glioma cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachnoid↗