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At least 847 records · Page 47Linked to original sources
PubMed2004

In vivo imaging of leukocyte trafficking in blood vessels and tissues.

Selective recruitment of blood-borne leukocytes to tissues and their proper positioning within them is crucial for the many integrated functions of the immune system. Intravital microscopy (IVM) techniques have been employed for more than a century to study these events at the single-cell level in living animals. Conventional video-based IVM allows the visualization of extremely rapid adhesion events at the interface between blood and tissue. Multiphoton IVM is a relatively new tool for imaging the slower dynamics of cell migration and cell-cell interactions in the extravascular space in three dimensions. Fueled by the burgeoning development of sophisticated fluorescent markers and increasingly powerful imaging tools, we are currently witnessing the emergence of a new field in immuno-imaging, in which leukocyte function and cell-cell communication is explored in a truly physiological context.

Animals↗
PubMed2002

Control of the AcrAB multidrug efflux pump by quorum-sensing regulator SdiA.

SdiA is an Escherichia coli protein that regulates cell division in a cell density-dependent, or quorum-sensing, manner. We report that SdiA also controls multidrug resistance by positively regulating the multidrug resistance pump AcrAB. Overproduction of SdiA confers multidrug resistance and increased levels of AcrAB. Conversely, sdiA null mutants are hypersensitive to drugs and have decreased levels of AcrB protein. Our findings provide a link between quorum sensing and multidrug efflux. Combined with previously published reports, our data support a model in which a role of drug efflux pumps is to mediate cell-cell communication in response to cell density. Xenobiotics expelled by pumps may resemble the communication molecules that they normally efflux.

Bacterial Proteins↗
PubMed1999

Sevoflurane induced suppression of inhibitory synaptic transmission between soma-soma paired Lymnaea neurons.

The cellular and synaptic mechanisms by which general anesthetics affect cell-cell communications in the nervous system remain poorly defined. In this study, we sought to determine how clinically relevant concentrations of sevoflurane affected inhibitory synaptic transmission between identified Lymnaea neurons in vitro. Inhibitory synapses were reconstructed in cell culture, between the somata of two functionally well-characterized neurons, right pedal dorsal 1 (RPeD1, the giant dopaminergic neuron) and visceral dorsal 4 (VD4). Clinically relevant concentrations of sevoflurane (1-4%) were tested for their effects on synaptic transmission and the intrinsic membrane properties of soma-soma paired cells. RPeD1- induced inhibitory postsynaptic potentials (IPSPs) in VD4 were completely and reversibly blocked by sevoflurane (4%). Sevoflurane also suppressed action potentials in both RPeD1 and VD4 cells. To determine whether the anesthetic-induced synaptic depression involved postsynaptic transmitter receptors, dopamine was pressure applied to VD4, either in the presence or absence of sevoflurane. Dopamine (10(-]5) M) activated a voltage-insensitive K(+) current in VD4. The same K(+) current was also altered by sevoflurane; however, the effects of two compounds were nonadditive. Because transmitter release from RPeD1 requires Ca(2+) influx through voltage-gated Ca(2+) channels, we next tested whether the anesthetic-induced synaptic depression involved these channels. Individually isolated RPeD1 somata were whole cell voltage clamped, and Ca(2+) currents were analyzed in control and various anesthetic conditions. Clinically relevant concentrations of sevoflurane did not significantly affect voltage-activated Ca(2+) channels in RPeD1. Taken together, this study provides the first direct evidence that sevoflurane-induced synaptic depression involves both pre- and postsynaptic ion channels.

Action Potentials↗
PubMed1993

Carotenoids and cancer: an update with emphasis on human intervention studies.

This article gives an overview of the current state of knowledge on the cancer preventive potential of carotenoids. Numerous retrospective and prospective epidemiological studies have shown that a high intake of carotenoid-rich fruits and vegetables is associated with a decreased risk of cancer at a number of common sites. For several other cancer sites, however, the epidemiological evidence is not very consistent. A number of mechanisms for the cancer preventive properties of carotenoids have been proposed. Conversion to retinol, possibly in posthepatic tissues, would allow an effect on cellular differentiation and proliferation, and on cell-to-cell communication. Antioxidant functions could prevent free radical-induced damage to cellular DNA and other macromolecules. Immunomodulatory effects could enhance immune surveillance in tumorigenesis. In addition, non-retinol-mediated effects of carotenoids on metabolism of carcinogens and cell-to-cell communication have been shown. Observational epidemiology cannot resolve whether associations are due to a specific carotenoid, or to an associated factor in fruits and vegetables, whereas interpretation of animal studies is hampered by uncertainties in extrapolation between species, more so because the metabolism of carotenoids in most animals differs notably from that in humans. Human intervention studies on biomarkers related to cancer risk and on cancer incidence are, therefore, necessary. Human intervention studies performed so far suggest that beta-carotene can affect carcinogenesis, though not at all stages and not at all cancer sites. Implications for future human intervention research are discussed.

Carotenoids↗
PubMed1986

Communication between primary endoderm and mesoderm for erythroblast differentiation in early chick blastoderm.

Blood islands are mesodermal cells which, in close association with the underlying endoderm, form blood cells and endothelium in the early embryo. The primary hypoblast (primary endoderm), separated from the epiblast of chick blastoderm at the full hypoblast stage, was labeled with 14C-protein hydrolysate. The labeled hypoblast was recombined with its denuded unlabeled epiblast. Radioautographs and uptake and incorporation measurements in the blood islands show that there is transport of label from the primary hypoblast to the erythroblasts or to some progenitor cell(s) of the erythroblasts in the epiblast. The observed cell communication between mesoderm and the endoderm is in concert with the description of the blood island cytoarchitecture in which mesodermal cells are making direct contact with the adjacent endodermal cells during erythroblast differentiation.

Animals↗
PubMed1978

Developmental stages in the formation of inverted gap junctions during turnover in the adult horseshoe crab, Limulus.

Stages leading to the formation of inverted gap junctions between certain basal replacement or interstitial cells in the mid-gut of adult Limulus can be followed by freeze-fracturing. Free, 13-nm EF intramembranous particles first appear to be organized into short linear arrays or small clusters of particles, which then become transformed into anastomosing particulate networks covering a considerable surface area. These subsequently become concentrated into smaller, more nearly circular, macular plaques of EF particles or PF pits. These EF particles, both when free or assembled into macular arrays, possess a central channel or pore. Numerous formed gap junctions are present in Limulus mid-gut, which suggests that cell-to-cell communication is an important feature of the mature tissue. The results show that arthropod tissues can be used to study the development of gap junctions not only in differentiating systems but also in adult tissues during normal cell turnover.

Animals↗
PubMed2005

Single short-term signal that enhances cooperative activity of old rat hepatocytes acts for several days.

Primary cultures of rat hepatocytes were studied in serum-free medium. Ultradian protein synthesis rhythm was used as a marker of overall cell synchronization and cooperation amongst the population. The level of synchronization was determined by amplitudes of the rhythm. Low synchronization of old rat hepatocytes can be enhanced by addition of either gangliosides or phenylephrine to the medium. Incubation of cultures with gangliosides lasted for 2.5 h, while action of phenylephrine was only for 2 min. The amplitude of protein synthesis rhythm was increased 1.5-2 times. In cultures transferred to a fresh normal medium, this increased amplitude was observed for at least 2-3 days. Thus, both gangliosides and phenyleprine are triggers, which, as shown earlier, initiated calcium-dependent processes in the cytoplasm. The results are discussed in the light of concept of the cell self-organization by a direct cell-cell communication.

Animals↗
PubMed2003

The immunological synapse.

The induction of a proper adaptive immune response is dependent on the correct transfer of information between antigen-presenting cells (APCs) and antigen-specific T cells. Defects in information transfer may result in the development of diseases, e.g. immunodeficiencies and autoimmunity. A distinct 3-dimensional supramolecular structure at the T cell/APC interface has been suggested to be involved in the information transfer. Due to its functional analogy to the neuronal synapse, the structure has been termed the "immunological synapse" (IS). Here, we review molecular aspects concerning IS formation, appearance, and cessation. In addition, proposed functions of the IS are discussed. The process of IS formation occurs in a sequential manner, initially causing a remarkable large-scale redistribution of a number of integral membrane and cytosolic proteins. At the T cell/APC interface the structure comprises in its nascent stage a non-random pattern of protein distribution. The protein pattern is regulated during development of the mature IS and is finally organized into concentric rings of co-receptors and adhesive molecules surrounding the T cell antigen receptor (TCR). The relocations of proteins are influenced by passive as well as active mechanisms. Considering the IS as a device enabling cell-cell communication, clarification of its exact function is of huge general as well as therapeutic interest.

Antigen-Presenting Cells↗
PubMed1999

Rapid and direct effects of pH on connexins revealed by the connexin46 hemichannel preparation.

pH is a potent modulator of gap junction (GJ) mediated cell-cell communication. Mechanisms proposed for closure of GJ channels by acidification include direct actions of H+ on GJ proteins and indirect actions mediated by soluble intermediates. Here we report on the effects of acidification on connexin (Cx)46 cell-cell channels expressed in Neuro-2a cells and Cx46 hemichannels expressed in Xenopus oocytes. Effects of acidification on hemichannels were examined macroscopically and in excised patches that permitted rapid (<1 ms) and uniform pH changes at the exposed hemichannel face. Both types of Cx46 channel were found to be sensitive to cytoplasmic pH, and two effects were evident. A rapid and reversible closure was reproducibly elicited with short exposures to low pH, and a poorly reversible or irreversible loss occurred with longer exposures. We attribute the former to pH gating and the latter to pH inactivation. Half-maximal reduction of open probability for pH gating in hemichannels occurs at pH 6.4. Hemichannels remained sensitive to cytoplasmic pH when excised and when cytoplasmic [Ca2+] was maintained near resting ( approximately 10(-7) M) levels. Thus, Cx46 hemichannel pH gating does not depend on cytoplasmic intermediates or a rise in [Ca2+]. Rapid application of low pH to the cytoplasmic face of open hemichannels resulted in a minimum latency to closure near zero, indicating that Cx46 hemichannels directly sense pH. Application to closed hemichannels extended their closed time, suggesting that the pH sensor is accessible from the cytoplasmic side of a closed hemichannel. Rapid closure with significantly reduced sensitivity was observed with low pH application to the extracellular face, but could be explained by H+ permeation through the pore to reach an internal site. Closure by pH is voltage dependent and has the same polarity with low pH applied to either side. These data suggest that the pH sensor is located directly on Cx46 near the pore entrance on the cytoplasmic side.

Algorithms↗
PubMedDate not supplied

Neuregulins and the neuromuscular system: 10 years of answers and questions.

The neuregulins were originally discovered in searches for the acetylcholine receptor-inducing activity (ARIA), glial growth factor (GGF), and a ligand for the oncogene neu (ErbB2/HER2). Neuregulin1 (NRG1)-mediated cell communication is critical in the central and peripheral nervous system, heart, breast, and other organ systems. This review will focus on the functions of NRG1s in the development and maintenance of the neuromuscular system and on the regulation of NRG1 signaling within this system. The roles of NRG1 signaling in the neuromuscular system are far more pervasive than contemplated when neuregulins were discovered 10 years ago. In fact, neuregulin-mediated cell communication plays an essential role in the biology of most components of the neuromuscular system--including motor and sensory neurons, muscle fibers, Schwann cells, and major specializations (neuromuscular synapses, muscle spindles, Golgi tendon organs, and peripheral nerves). It is argued here that while NRG1 proteins are indeed "ARIA" and "GGF", their involvement in regulating synapse-specific transcription and Schwann cell development is more complex than originally proposed. It is also argued that NRG1 isoforms differ in their signaling properties and that these differences tailor specific isoforms for specific signaling tasks; for example, some NRG1 isoforms may be specialized for paracrine signaling and others for juxtacrine signaling. In the first 10 years of neuregulin research there has been much progress in understanding the actions of neuregulins in shaping and maintaining the neuromuscular system. However, major questions, old and new, remain unanswered; and the second 10 years promises to be at least as exciting as the first.

Animals↗
PubMed1993

Studies on the modulating effects of retinoic acid and retinol acetate using dye transfer and metabolic cooperation assays.

The effects of retinoic acid and retinol acetate on gap junctional communication were examined in two in vitro tests. Rat liver epithelial cell line IAR 203 was used for dye transfer assays, and hamster lung fibroblast V79 cells were used for metabolic cooperation assays. A reversible dose-dependent inhibition of dye transfer was detected after a 1-hr treatment with retinoic acid or retinol acetate at concentrations ranging from 10 to 50 microM. On the other hand, enhancement of dye transfer was observed after a 24-hr treatment with retinoic acid at 0.1 microM. A dose-dependent inhibition of metabolic cooperation was obtained with retinoic acid at noncytotoxic concentrations ranging from 5 to 50 microM. Retinoids and TPA (1 ng/ml) acted synergistically in their inhibition of cell communication. Thus, the assays appear to be complementary: the dye transfer assay was useful in studying the time course and the reversibility of the inhibition or enhancement of dye transfer, whereas the metabolic cooperation assay was effective in quantifying the inhibitory effect of TPA or retinoids and interactions between them.

Animals↗
PubMed1992

Activity of diverse tumor promoters in a keratinocyte co-culture model of initiated epidermis.

The suppression of focal growth of initiated mouse keratinocytes by co-culture with normal keratinocytes can be overcome by treatment of co-cultures with the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). This keratinocyte co-culture model was developed as an analog of initiated mouse epidermis to facilitate the study of tumor promotion in cell culture. A number of promoters of TPA-type [those with protein kinase C (PKC) as receptor] were compared to non-TPA-type promoters for activity in the keratinocyte co-culture model. The TPA-type promoters teleocidin and aplysiatoxin show comparable activity to that of TPA. Exposure of co-cultures to oleoyl-2-acetylglycerol, a diacylglycerol activator of PKC, also induces focal outgrowth of initiated cells, suggesting that PKC is likely to be involved in the mechanism of action of these compounds. However, the involvement of alternative pathways (not involving PKC directly) for clonal selection are evident since the non-TPA-type promoters okadaic acid, staurosporine and thapsigargin are also active in the assay. Thus, the keratinocyte co-culture model differs from fibroblast models of normal and neoplastic co-cultures in which only TPA-type promoters are active. In further contrast to certain fibroblast co-cultures, TPA does not inhibit cell-cell communication under conditions that suppress focus formation. Taken together with previous data, we conclude that the keratinocyte co-culture model may have broad application for detecting skin tumor promoters, and may be useful for dissecting the mechanism by which normal epidermal cells suppress the growth of initiated cells.

Animals↗
PubMed2004

Nanotubular highways for intercellular organelle transport.

Cell-to-cell communication is a crucial prerequisite for the development and maintenance of multicellular organisms. To date, diverse mechanisms of intercellular exchange of information have been documented, including chemical synapses, gap junctions, and plasmodesmata. Here, we describe highly sensitive nanotubular structures formed de novo between cells that create complex networks. These structures facilitate the selective transfer of membrane vesicles and organelles but seem to impede the flow of small molecules. Accordingly, we propose a novel biological principle of cell-to-cell interaction based on membrane continuity and intercellular transfer of organelles.

Actins↗
PubMed2000

Probing the function of connexin channels in primary tissues.

Connexin channels provide for a widespread mechanism of cell-to-cell cross-talk within primary tissues, which is mediated by intercellular exchanges of cytoplasmic ions and molecules. Experimental and clinical studies have recently provided evidence that these exchanges are most likely to play multiple roles, which are critical for the proper development and function of primary tissues. There is also increasing evidence that major clinical disorders may result when the formation and function of connexin channels are altered. Still, the physiological functions that the cell-to-cell communication mediated by connexin channels subserve in most primary tissues are still uncertain. Here, I review two approaches that may aid in identifying these specific functions.

Animals↗
PubMed2006

Tumor-derived Cyr61(CCN1) promotes stromal matrix metalloproteinase-1 production and protease-activated receptor 1-dependent migration of breast cancer cells.

Matrix metalloproteinases (MMPs) play a central role in remodeling the tumor-stromal microenvironment. We recently determined that stromal-derived MMP-1 also acts as a signaling molecule by cleaving protease-activated receptor 1 (PAR1) to cause breast cancer cell migration and invasion. Here, we show that ectopic PAR1 expression induces expression of the angiogenic factor Cyr61(CCN1) in breast cancer cells. The tumor-derived Cyr61 acts as an invasogenic signaling molecule that induces MMP-1 expression in adjacent stromal fibroblasts. Gene silencing of Cyr61 in breast cancer cells suppresses MMP-1 induction in stromal fibroblasts resulting in a major loss in migration of the cancer cells toward the fibroblasts. Cyr61-dependent loss of migration was complemented by exogenous MMP-1 and required the presence of the functional PAR1 receptor on the breast cancer cells. These results suggest that interrupting tumor-stromal cell communication by targeting Cyr61 may provide an alternative therapeutic approach for the treatment of invasive breast cancer.

Animals↗
PubMed1988

Metastatic capacity and intercellular communication between normal cells and metastatic cell clones derived from a rat mammary carcinoma.

Three highly metastatic clones and two weakly metastatic clones were obtained from a spontaneously arising mammary carcinoma in an SHR rat. The difference in their capacity to generate metastatic ability was recognized when the tumor cells were implanted s.c. but not when they were implanted i.v. This evidence possibly indicates that the difference in the metastatic capacity of these clones is caused by different potential for detachment from the primary site and for intravasation during the various steps of metastasis. There are no differences between highly and weakly metastatic clones with regard to their in vitro growth characteristics (doubling time, saturation density, plating efficiency, etc.), homotypic aggregation, and adhesiveness to plastic matrices and fibroblast monolayers. Therefore, we used a dye transfer method to examine the relationship between the metastatic capacity of tumor cells and the capacity of tumor cells to make junctional communication with normal fibroblasts. We found that the incidence of intercellular communication between weakly metastatic clone cells and fibroblasts (derived from normal s.c. tissues and tumor tissues) was significantly higher than that between highly metastatic clone cells and fibroblasts. These results suggest that junctional communication between tumor cells and normal fibroblasts may play a part in the early stage of cancer metastasis.

Animals↗
PubMed2004

Suppression of drug-resistant Staphylococcal Infections by the quorum-sensing inhibitor RNAIII-inhibiting peptide.

Staphylococcus aureus and S. epidermidis are major causes of infection related to biofilm formed on indwelling medical devices. Such infections are common causes of morbidity and mortality and, because of biofilm resistance to antibiotics, are difficult to treat. The RNAIII-inhibiting peptide (RIP) (YSPWTNF-NH2) inhibits the pathogenesis of staphylococci by disrupting bacterial cell-cell communication (known as "quorum sensing"). Using a vascular-graft rat model, we show that RIP, applied locally and systemically, can completely inhibit drug-resistant S. aureus and S. epidermidis biofilms. The present study provides the first direct demonstration that interfering with cell-cell communication by use of a quorum-sensing inhibitor can eliminate medical device-associated staphylococcal infections. We suggest that medical devices could be coated with RIP to prevent infections, including those by antibiotic-resistant staphylococcal strains.

Animals↗
PubMed2003

Temporal relationships between FSH receptor, type 1 insulin-like growth factor receptor, and aromatase expression during FSH-induced differentiation of bovine granulosa cells maintained in serum-free culture.

A serum-free culture system has been developed in ruminants that allows gonadotrophin-responsive induction of oestradiol (E2) production by non-differentiated granulosa cells (GC) from small antral follicles. Critical determinants are dose of FSH and insulin-like growth factor (IGF), and the plating density of the GC. Over the first 16 h of culture when cells remained as a dispersed monolayer, expression declined in FSH receptors (FSHr) (P <0.001), IGF type 1 receptor (IGF-1r) (P <0.08) and p450 arom (CYP19, P <0.001). Characteristic GC clusters formed from 16 h and further enlarged between 24 and 48 h, accompanied by marked increases in FSHr (P <0.01), IGF-1r (P <0.05), and p450 arom (P <0.01) expression, and preceded induction and subsequent peak E2 production, at 96 and 144 h, respectively (P <0.01). In conclusion, isolation and dispersion of GC appears to induce reversion to an immature state resulting in loss of receptor expression. Re-establishment of cell-cell communications in the presence of FSH and IGF results in receptor up-regulation and induction of cellular differentiation.

Animals↗