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PubMed1984

Inhibition of cell communication between Balb/c 3T3 cells by tumor promoters and protection by cAMP.

The effect of phorbol ester tumor promoters on the communication between individual cells in confluent culture was studied using a fluorescent dye transfer method. Cell-cell communication between mouse Balb/c 3T3 cells and between Chinese hamster V79 cells was inhibited almost completely by tumor-promoting phorbol esters, but not by nonpromoting derivatives; the effect was reversed upon removal of the promoter. Intercellular communication between Balb/c 3T3 cells, but not Chinese hamster V79 cells, was increased significantly in the presence of dbcAMP and caffeine, and these compounds counteracted the effects of tumor promoters. Inhibition of cell communication by phorbol esters appears to be receptor-mediated, since specific binding of 3H-phorbol-12,13-dibutyrate to Balb/c 3T3 cells was inhibited only by compounds that also inhibit intercellular dye transfer. A study with cycloheximide suggests that the reversible inhibition of intercellular communication by phorbol esters may not need de novo protein synthesis, while upregulation of communication by cAMP requires protein synthesis.

Animals↗
PubMed2002

Cell-to-cell communication in response of E. coli cells at different phases of growth to low-intensity microwaves.

Effects of millimeter waves (MMW) at the frequency of 51.755 GHz were studied in logarithmic and stationary E. coli cells at various cell densities. The changes in the genome conformational state (GCS) were analyzed by the method of anomalous viscosity time dependence (AVTD). Before lysis, the cells were adjusted to the cell density of 4x10(7) cells/ml and all AVTD measurements were run at this cell density. Stationary cells responded to MMW by increase in AVTD, while the same MMW exposure decreased AVTD in logarithmic cells. MMW effects depended on cell density during exposure and were stronger for stationary cells. The observed dependence on cell density suggested a cell-to-cell communication between cells during exposure to microwaves. Decrease in power density (PD) resulted in more striking differences between responses at different cell densities. The data provided evidence that intercellular communication in response to MMW depended on cell status and PD of microwaves. The MMW effects were studied in more detail at low intensity of 10(-17) W/cm(2) in the range of cell densities 4x10(7) to 8x10(8) cells/ml. The obtained sigmoid-like dependence of MMW effect on cell density saturated at approximately 5x10(8) cells/ml. The dependence of MMW effect on cell density was very similar in this study and in previous studies with weak extremely low frequency (ELF) electromagnetic fields (EMF). The data suggested that cell-to-cell communication might be involved in response of cells to weak EMF of various frequency ranges.

Cell Communication↗
PubMed1988

Contrasting duration of inhibition of cell-cell communication in primary mouse epidermal cells by phorbol 12,13-dibutyrate and by bryostatin 1.

The bryostatins, macrocyclic lactones isolated on the basis of their antineoplastic activity, activate protein kinase C in vitro and inhibit phorbol ester binding to the enzyme. In intact cells, the bryostatins induce some phorbol ester responses, such as neutrophil activation, but paradoxically they not only fail to induce other responses, e.g., differentiation in HL-60 promyelocytic leukemia cells, but actually block response to the phorbol esters. We compare here bryostatin I and phorbol 12,13-dibutyrate as inhibitors of cell-cell communication in cultured primary mouse epidermal cells. Like phorbol 12,13-dibutyrate, bryostatin I at nanomolar concentrations markedly inhibited cell coupling. It differed from the phorbol esters, however, in that its action was more transient. By 4 h of incubation bryostatin 1 caused little inhibition of coupling. Moreover, coincubation of bryostatin 1 and phorbol 12,13-dibutyrate gave no greater response at this time than that found for bryostatin 1 alone. Time-dependent inhibition of the protein kinase C pathway could account for many of the observed differences between the actions of the phorbol esters and bryostatin 1.

Animals↗
PubMed1984

Cell-to-cell communication in monolayers of epithelioid cells (MDCK) as a function of the age of the monolayer.

We explore the existence of cell-to-cell communication in monolayers of MDCK cells plated at high densities so that they form a continuous monolayer in a few minutes. Lucifer Yellow CH is injected in the cytoplasm of a given cell by using a glass microelectrode with a fine tip (ca. 100 M omega) and passing square pulses of current of 1.0 nA that last 10 msec, every 20 msec, during 1 to 3 min. We then examine the monolayer with fluorescence microscopy. In 27 out of 111 cells injected during the first 4 to 15 hr after plating, the dye was transferred to neighboring cells. Electron micrographs of freeze-fracture replicas prepared at this time, show that 20 to 25% of the lateral surfaces present the aggregates of intramembrane particles typical of gap junctions. These early hours correspond to the formation of occluding junctions and polarization into an apical and a basolateral domain of the plasma membrane (Cereijido, Meza & Martínez-Palomo, 1981). Cell-to-cell coupling then decreases sharply and, in the period between the 1st and 3rd day (mature monolayers), only 4 out of 49 injected cells were able to transfer the dye to their neighbors in the monolayers. No image of gap junctions was found in freeze-fracture replicas of mature monolayers. The degree of coupling between cells, as well as the number of cells coupled to the injected one, were highly variable. The lack of coupling between cells in mature monolayers observed in this article with Lucifer Yellow CH and electron microscopy is in keeping with the absence of electrical coupling observed in a previous work (Stefani & Cereijido, 1983). The transient existence of communicating junctions observed in monolayers of MDCK cells is similar to that described in the literature for embryo tissues during development.

Animals↗
PubMed1995

Cell-to-cell communication in osteoblastic networks: cell line-dependent hormonal regulation of gap junction function.

We have characterized the distribution, expression, and hormonal regulation of gap junctions in primary cultures of rat osteoblast-like cells (ROBs), and three osteosarcoma cell lines, ROS 17/2.8, UMR-106, and SAOS-2, and a continuous osteoblastic cell line, MC3T3-E1. All cell lines we examined were functionally coupled. ROS 17/2.8 were the more strongly coupled, while ROB and MC3T3-E1 were moderately coupled and UMR-106 and SAOS-2 were weakly coupled. Exposure to parathyroid hormone (PTH) for 1 h increased functional coupling in ROB cells in a concentration-dependent manner. Furthermore, PTH(3-34), an analog of PTH with binds to the PTH receptor and thus attenuates PTH-stimulated cAMP accumulation, also attenuated PTH-stimulated functional coupling in ROB. This suggests that PTH increases functional coupling partly through a cAMP-dependent mechanism. A 1 h exposure to PTH did not affect coupling in ROS 17/2.8, UMR-106, MC3T3-E1, or SAOS-2. To examine whether connexin43 (Cx43), a specific gap junction protein, is present in functionally coupled osteoblastic cells, we characterized Cx43 distribution and expression. Indirect immunofluorescence with antibodies to Cx43 revealed that ROS 17/2.8, ROB, and to a lesser extent MC3T3-E1 and UMR-106, expressed Cx43 immunoreactivity. SAOS-2 showed little if any Cx43 immunoreactivity. Cx43 mRNA and Cx43 protein were detected by Northern blot analysis and immunoblot analysis, respectively, in all cell lines examined, including SAOS-2. Our findings suggest that acute exposure to PTH regulates gap junction coupling, in a cell-line dependent manner, in osteoblastic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1999

Regulation of cell-cell communication in rat bone cells: the effect of phorbol esters.

The skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is a potent inhibitor of gap junctional intercellular communication. In the present study, the inhibition of cell-cell communication by TPA has been investigated in primary bone cells from newborn rat calvaria, with an emphasis on the involvement of intracellular pH (pH(i)) and cytosolic calcium ([Ca(+2)](i)) in this process. The results show that TPA (5 x 10(-)(8) M) caused a complete inhibition of intercellular communication within 40-60 min. The intercellular communication was fully restored after overnight incubation in the presence of TPA. This effect was found to be associated with an elevation of pH(i). However, neither an increase of pH(i) alone nor exposure to TPA, under conditions preventing pH(i)-shift, were found to affect intercellular communication. It is suggested that the inhibition of intercellular communication, in the presence of TPA, depends on the pH(i)-shift itself rather than on the absolute value of pH(i). In addition, elevation of cytosolic calcium by ionomycin led to the termination of intercellular communication after 30 min. This inhibitory effect was abolished when the cells were incubated for overnight with TPA and then intracellular calcium was elevated by the addition of ionomycin. These results indicate that shift of pH(i) and the increase of intracellular calcium are involved in repression of intercellular communication by TPA.

Animals↗
PubMed1985

Cell-to-cell communication properties of Auerbach's plexus cell in culture.

Cultured Auerbach's plexus cells are coupled by low-resistance channels that permit the cell-to-cell passage of electrical current and fluorescein dye. The permeability of their intercellular junctions is blocked by the increased concentration of cytoplasmic Ca2+, thereby indicating that the cell-to-cell communication properties in cultured Auerbach's plexus cells are modulated by the cytoplasmic level of Ca2+.

Calcium↗
PubMed2001

Cell-cell communication in the vessel wall.

Intercellular communication between cells within the blood vessel wall plays an important role in the control of artery diameter. The endothelial cells lining the lumen of arteries can evoke smooth muscle hyperpolarization both by the release of a factor (EDHF) and by direct cell-cell coupling through gap junctions. Hyperpolarizing current can spread rapidly to cause widespread vasodilatation, and thus increase blood flow to that segment. In addition to the spread of current, small molecules, such as Ca2+, can also pass between cells, but at a much reduced rate. Instead of co-ordinating changes in diameter, intercellular Ca2+ signalling acts to amplify and, in special cases, modulate vascular responses. Together, direct cell-cell communication enables the blood vessel wall to act as a functional syncytium, which is influenced by surrounding tissues and nerves, and blood constituents.

Animals↗
PubMed1977

Cell-to-cell communication and myogenesis.

Cell-to-cell communication was characterized in prefusion chick embryo myoblast cultures, and it was determined that the prefusion myoblasts can interact via gap junctions, ionic coupling, and metabolic coupling. The biological relevance of this communication was supported by the detection of gap junctions between myoblasts in embryonic muscle. Communication was also examined in fusion-arrested cultures to determine its potential relationship to fusion competency. In cultures that were fusion arrested by treatment with either 1.8 mM ethyleneglycolbis-(beta-aminoethyl ether)N,N'-tetraacetic acid (EGTA), 3.3 X 10(-6) M 5-bromodeoxyuridine (BUdR), or 1 microgram/ml cycloheximide (CHX), both gap junctions and ionic coupling were present. Therefore, it is possible to conclude that cell communication is not a sufficient property by itself, to generate fusion between myob-asts. The potential role of communication in myogenesis is discusssed with respect to these observations.

Cell Communication↗
PubMed2025

scACCorDiON: a clustering approach for explainable patient level cell-cell communication graph analysis.

MOTIVATION: Combining single-cell sequencing with ligand-receptor (LR) analysis paves the way for the characterization of cell communication events in complex tissues. In particular, directed weighted graphs naturally represent cell-cell communication events. However, current computational methods cannot yet analyze sample-specific cell-cell communication events, as measured in single-cell data produced in large patient cohorts. Cohort-based cell-cell communication analysis presents many challenges, such as the nonlinear nature of cell-cell communication and the high variability given by the patient-specific single-cell RNAseq datasets. RESULTS: Here, we present scACCorDiON (single-cell Analysis of Cell-Cell Communication in Disease clusters using Optimal transport in Directed Networks), an optimal transport algorithm exploring node distances on the Markov Chain as the ground metric between directed weighted graphs. Benchmarking indicates that scACCorDiON performs a better clustering of samples according to their disease status than competing methods that use undirected graphs. We provide a case study of pancreas adenocarcinoma, where scACCorDion detects a sub-cluster of disease samples associated with changes in the tumor microenvironment. Our study case corroborates that clusters provide a robust and explainable representation of cell-cell communication events and that the expression of detected LR pairs is predictive of pancreatic cancer survival. AVAILABILITY AND IMPLEMENTATION: The code of scACCorDiON is available at https://scaccordion.readthedocs.io/en/latest/. and https://doi.org/10.5281/zenodo.15267648. The survival analysis package can be found at https://github.com/CostaLab/scACCorDiON.su.

Humans↗
PubMed1983

Cell-to-cell communication in rat pancreatic islet monolayer cultures is modulated by agents affecting islet-cell secretory activity.

Single islet cells in monolayer cultures of neonatal rat pancreas were microinjected with the fluorescent dye Lucifer Yellow CH and the cultures were observed by combined phase contrast and fluorescent microscopy. The dye spread from an injected cell directly into neighboring islet cells, and successive microinjections of dye into different cells defined territories comprised of 2-6 communicating cells. The number of communicating cells could be modulated by addition to the cultures of different agents known to affect islet cell secretory activity. Cell communication was significantly increased by a high (16.7 mM) glucose concentration, by the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 0.1 mM), and by the calcium ionophore, A23187. The effect of A23187 was transient and dose-dependent. Somatostatin (1 microgram/ml) significantly inhibited cell communication. These results demonstrate that cell-to-cell communication may participate in the regulation of islet cell secretory activity.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Cell-to-cell communication in cultured Sertoli cells.

Junctional transfer of ions in monolayer primary cultures of Sertoli cells has been studied by using conventional techniques. Cells were extensively electrically coupled. Membrane voltage displacements caused by the injected current pulses were measured at variable interelectrode distance. Data analyses were based on a thin-sheet model for current flow (Jongsma and van Rijn, 1972) and yielded a generalized space constant of 248 microns and an internal resistivity of 1.7 kOhm.cm in standard medium. Electrical coupling was inhibited by A23187 Ca2+ ionophore (5 microM).

Animals↗
PubMed1987

Prolactin enhances cell-to-cell communication among beta-cells in pancreatic islets.

To determine the role of prolactin in increasing junctional communication among islet beta-cells, we studied dye coupling in pancreatic islets exposed to elevated levels of prolactin in vivo and in vitro. Islets were isolated from rats immediately after lactation or from rats bearing mammosomatotropic tumors (MtTW15), conditions involving high levels of prolactin (either 5-fold or 1000-fold control levels, respectively). When beta-cells were microinjected with the gap junction permeant dye Lucifer yellow CH, the mean number of dye-coupled cells per injection was approximately 10-fold greater than in islets from virgin control rats. As a more direct test of the effects of prolactin on beta-cell coupling, islets isolated from virgin rats were treated for 90 min with 500 ng/ml rat prolactin in the presence of low glucose (2.8 mM) and were microinjected with dye. The mean number of dye-coupled cells per injection increased by 6.7-fold over controls with low glucose, demonstrating a direct effect of prolactin on beta-cell coupling. In vitro treatment with high glucose (16.7 mM) resulted in a 2.7-fold increase in dye-coupled cells per injection. We discuss the possible relationship between the effects of glucose and of prolactin on coupling.

Animals↗
PubMed1995

Ultrastructural evidence of cell communication between epithelial dark cells and melanocytes in vestibular organs of the human inner ear.

BACKGROUND: The possibility of interaction between epithelial dark cells and melanocytes in the mammalian inner ear has been pointed out because of their morphological and biochemical characteristics, although very few studies have dealt directly with communication between these two types of cells. We investigated the dark cell area of human vestibular organs in order to clarify the ultrastructural evidence for cell interaction between epithelial dark cells and melanocytes. METHODS: All of the material was obtained from vestibular schwannoma operations. Paraffin sections were stained with hematoxylin and eosin (H&E) and by the Fontana-Masson technique. Other paraffin sections were also stained immunohistochemically for S-100 protein. Glutaraldehyde fixed specimens were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: Light microscopy revealed melanin pigment granules in the cytoplasm of epithelial dark cells. Melanocytes in the subepithelial layer stained positively for S-100 protein. The presence of intraepithelial melanocytes was confirmed by the presence of cell profiles with a large number of melanin pigment granules and S-100 protein in the cytoplasm. SEM showed that the dark cells had a pentagonal surface with microvilli on the apical surface edge. They had complicated structures at the basal portion of their cytoplasm. Melanocytes extending cytoplasmic processes to adjacent areas were observed under the dark cells. TEM showed that the dark cells were tightly linked by junctional complexes in the upper lateral portion of their cytoplasmic membrane and interdigitated by lateral infoldings. Compound melanosomes (phagosomes or secondary lysosomes) found in the cytoplasm of the dark cells contained poorly pigmented melanosomes with a periodic internal structure. Gap junctions were clearly showed between adjacent melanocytes in the subepithelial layer. CONCLUSIONS: The characteristic substructures of dark cells and melanocytes suggested the presence of intimate cell interaction between these two types of cells in the vestibular organs of the human inner ear, although it is not clear at this stage whether such cell interaction is specific only for patients with vestibular schwannoma. Dark cells and melanocytes form a cell community that serves to maintain homeostasis in vestibular organs through communication in which cell information obtained by both dark cells and melanocytes serves to facilitate the system.

Adult↗
PubMed1998

Parathyroid hormone effect on cell-to-cell communication in stromal and osteoblastic cells.

We characterized the formation and regulation of the gap junction in calvarial osteoblasts and in a series of subtypes from marrow stromal cells. The stromal cells included osteogenic, chondro-osteogenic, and endothelial cells. The cell coupling was measured by using fluorescence dye injected into single cells, and its migration to neighboring cells was measured. The functional coupling of cells was highly expressed by the osteoblastic cells. This process is mediated through fast changes in intracellular Ca+2 levels. Calcium ionophore (A 23,187) demonstrated an uncoupling effect on the cells. In addition, the exposure of the cells to the parathyroid hormone increased the formation of the gap junction complex; the highest level was demonstrated in the osteoblastic cells.

Bone Marrow Cells↗