Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “intercellular communication”

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 1,261 records · Page 70Linked to original sources

Control of immune responses by trafficking cell surface proteins, vesicles and lipid rafts to and from the immunological synapse.

Supramolecular clusters at the immunological synapse provide a mechanism for structuring complex communication networks between cells of the immune system. Regulating intra- and intercellular trafficking of proteins and lipids to and from the immunological synapse provides an additional level of complexity in determining the functional outcome of immune cell interactions. An emergent principle is that molecules requiring tightly regulated cell surface expression, e.g. negative regulators of cell activation or molecules promoting cytotoxicity, are trafficked to the immunological synapse from intracellular secretory as required lysosomes. Many molecules required for the early stages of the intercellular communication are already present at the cell surface, sometimes in lipid rafts, and are rapidly translocated laterally to the intercellular contact. Our understanding of these events critically depends on utilizing appropriate technologies for probing supramolecular recognition in live cells. Thus, we also present here a critical discussion of the technologies used to study lipid rafts and, more broadly, a map of the spatial and temporal dimensions covered by current live cell physical techniques, highlighting where advances are needed to exceed current spatial and temporal boundaries.

Animals↗

Epithelial-mesenchymal interactions in postnatal rat lung growth.

Epithelial-mesenchymal interactions have been implicated in epithelial cell differentiation in fetal lung. The role of such intercellular communication during postnatal lung growth is now evaluated to correlate intercellular contacts with cell division and with biochemical function of epithelial and interstitial cells. Sexed newborn rats, killed at frequent intervals to 8 weeks, received 3H-thymidine 1 h before death. A period of rapid cell proliferation between 3 and 10 days involved a five-fold increase in labeling index of both interstitial and type 2 epithelial cells. Hydroxyproline levels increased rapidly as interstitial cell division slowed, and epithelial growth was associated with elevated levels of disaturated phosphatidylcholine. Compared to the time of birth when epithelial cell division was slow, continuous basement membrane (BM) was more frequently found beneath type 2 cells during the postnatal proliferative phase, and fewer foot processes (FP) penetrated the BM; type 1 cells had few FP and uninterrupted BM. The number of intercellular contacts between type 2 cells and interstitial cells, one per two epithelial cell profiles at birth, decreased rapidly during the postnatal proliferative phase. There was a subsequent increase between 2 and 4 weeks that may reflect postmitotic epithelial differentiation. These observations support the hypothesis that transfer of mesenchymal factors may be important in the control of pulmonary epithelial growth and differentiation. The low incidence of cell-cell contacts seen after 4 weeks, one per five epithelial cell profiles, may reflect base levels of communication necessary to retain type 2 cell function in a resting cell population.

Animals↗

Involvement of gap junctional communication in myogenesis.

Cell-to-cell communication plays important roles in development and in tissue morphogenesis. Gap junctional intercellular communication (GJIC) has been implicated in embryonic development of various tissues and provides a pathway to exchange ions, secondary messengers, and metabolites through the intercellular gap junction channels. Although GJIC is absent in adult skeletal muscles, the formation of skeletal muscles involves a sequence of complex events including cell-cell interaction processes where myogenic cells closely adhere to each other. Much experimental evidence has shown that myogenic precursors and developing muscle fibers can directly communicate through junctional channels. This review summarizes current knowledge on the GJIC and developmental events involved in the formation of skeletal muscle fibers and describes recent progress in the investigation of the role of GJIC in myogenesis: evidence of gap junctions in somitic and myotomal tissue as well as in developing muscle fibers in situ, GJIC between perfusion myoblasts in culture, and involvement of GJIC in cytodifferentiation of skeletal muscle cells and in myoblast fusion. A model of intercellular signaling is proposed where GJIC participates to coordinate a multicellular population of interacting myogenic precursors to allow commitment to the skeletal muscle fate.

Animals↗

PDGF regulates gap junction communication and connexin43 phosphorylation by PI 3-kinase in mesangial cells.

BACKGROUND: Gap junctional intercellular communication (GJIC) plays an important role in the regulation of cell growth, migration, and differentiation. Ultrastructural and histochemical studies indicate the existence of a high density of gap junctions among mesangial cells (MCs), but little is known about their regulation. Because of the close link between growth and GJIC, we examined how platelet-derived growth factor (PDGF) may affect GJIC in cultured MCs. METHODS: MCs were exposed to PDGF in the presence or absence of phosphatidylinositol 3' kinase (PI3K) inhibitors, and GJIC was evaluated by the transfer of Lucifer yellow. The gap junction protein connexin43 (Cx43) was examined by immunohistochemistry, immunoprecipitation, and Western blot. RESULTS: The addition of PDGF into MC culture caused a rapid and transient inhibition of GJIC, with maximal inhibition (80%) occurring 15 minutes after PDGF exposure and returning to control levels after 90 minutes. This action of PDGF could be largely prevented by pretreatment of MCs with the PI3K inhibitor LY294002. Immunochemical staining showed that PDGF did not alter the localization and distribution of Cx43. Immunoprecipitation studies demonstrated that PDGF induced a rapid and transient increase of tyrosine phosphorylation of Cx43 protein, which was dose dependent and in accordance with the time course of the disruption of GJIC. PDGF also elicited activation of extracellular signal-regulated kinase (ERK). Using two structurally unrelated PI3K inhibitors, wortmanin and LY294002, both tyrosine phosphorylation of Cx43 and activation of ERK stimulated by PDGF were largely blocked. CONCLUSION: These results suggest that PDGF abrogates GJIC function in MCs via the PI3K-dependent signaling pathway. Disruption of GJIC by PDGF could be one mechanism by which PDGF modulates MC behavior. Participation of PI3K in the regulation of GJIC demonstrates the complex coordination of molecular events that accompany MC mitogenesis.

Animals↗

Vascular gap junctional communication is increased in mineralocorticoid-salt hypertension.

Cells rely on gap junctions for intercellular communication, which is important for growth and contractility. For example, gap junctional communication in the uterus increases near parturition, with a concomitant increase in oscillatory contractions. Because arterial responsiveness to contractile agonists is increased in hypertension, we tested the hypothesis that gap junctional communication is increased in hypertension. We examined thoracic aortas from deoxycorticosterone acetate (DOCA)-salt hypertensive and sham normotensive rats using isolated tissue baths and Western blotting techniques. The concentration of 5-hydroxytryptamine necessary to produce a threshold response was significantly lower in aortas from DOCA-salt (4 nmol/L) compared with sham (100 nmol/L) rats; this was also true for norepinephrine and KCl. In these same aortas, the appearance of spontaneous oscillatory contractions, which are sensitive to the gap junctional inhibitor heptanol (0.3 mmol/L), was more frequent in DOCA-salt arteries (93% versus 14% in sham). Heptanol (1 mmol/L) normalized the DOCA-salt aortic contraction to 5-hydroxytryptamine to levels similar to those of the response of the sham aorta in the presence of heptanol. Western analyses revealed that the density of connexin43 immunoreactivity, the connexin being a constituent of gap junctions, was found to be threefold more abundant in aortic homogenates of DOCA-salt rats compared with that of sham rats. This finding supports the hypothesis that gap junctional communication is increased in hypertension, at least at the protein level. We speculate that this increase results in a portion of the increased vascular reactivity and appearance of contractile oscillations in vascular smooth muscle.

Animals↗

Alterations in cell-cell communication in human papillomavirus type 16 (HPV16) transformed rat myoblasts.

A reduction of gap-junctional intercellular communication (GJIC) often accompanies neoplastic transformation. The present work demonstrates that transformation by the oncogenic human DNA virus, human papilloma virus 16(HPV16), also reduces GJIC between L6 rat myoblasts. HPVs are associated with anogenital cancers, the incidence of which is increasing in HIV positive patients of both sexes. Using videofluorescence imaging of Fura-2 loaded cells a lack of GJIC between transformed HPV16-L6 cells was first indicated by uncoordinated brief [Ca2+]i spikes in clusters of DMSO-treated HPV16-L6 cells instead of the synchronous, sustained [Ca2+]i surges in clusters of DMSO-treated L6 cells. Reduced GJIC between HPV16-L6 cells was demonstrated directly by a much reduced transfer of lucifer yellow dye from HPV16-L6 cells, which had been loaded with the dye through electroporation with an EPIZAP II in situ electroporator, to neighbouring nonelectroporated HPV16-L6 cells. One reason for this reduced GJIC between HPV16-L6 cells could have been their dramatically enhanced activity of membrane-associated PKC which is known to phosphorylate connexins and down-regulate gap junctions. However, the main reason was the viral-induced inhibition of the expression of a major gap junction component, Cx43 (Connexin 43), in the transformed myoblasts.

Animals↗

Molecular cloning, expression analysis, and functional characterization of connexin44.1: a zebrafish lens gap junction protein.

The connexin family of genes codes for proteins that oligomerize into a connexon of six subunits to form one half of the gap junction channel. Gap junctions are plasma membrane structures that mediate intercellular communication by joining the cytoplasm of two cells, allowing the passage of small molecules and metabolites, and contributing significantly to the maintenance of tissue homeostasis. The signaling mediated by these junctions appears to be necessary for the correct timing of key developmental events. This communication is especially important in the avascular lens where the intercellular passage of metabolites, second messengers, and ions is necessary to maintain the correct ionic balance in the lens fibre cells, and prevent cataract formation. To characterize the role that the connexin genes play in development, a novel connexin was cloned from zebrafish. A genomic clone was isolated that contained a 1,173 base open reading frame. The nucleotide sequence in this open reading frame shows extensive sequence similarity to mouse connexin50 (Cx50), chicken Cx45.6, sheep Cx49, and human Cx50. The protein encoded by this open reading frame contains 391 amino acids, with a predicted molecular weight of 44.1 kDa and a typical connexin transmembrane topology. By using the LN54 radiation hybrid panel, the Cx44.1 gene was mapped to linkage group 1. Whole-mount in situ hybridization and Northern blot analyses were performed on zebrafish embryos at various developmental stages to characterize the developmental expression of the Cx44.1 message. The ocular lens was the only tissue in which Cx44.1 transcripts were detected. The transcripts were first detected in the lens around 24 hr post fertilization and remained detectable until 120 hr post fertilization. Electrophysiological analysis of Cx44.1 channels revealed gating properties that were virtually identical to the mouse and chicken orthologues of Cx44.1.

Animals↗

Associations between the neuroendocrine and immune systems.

Organisms respond to infection with complex adaptations involving bidirectional communication between the immune and neuroendocrine systems. The idea of intercellular communication between the neuroendocrine and immune systems via common signal molecules has provided a conceptual framework for such crosstalk. The studies to date show that cells of the immune system contain receptors for neuroendocrine hormones and can also be considered a source of pituitary and hypothalamic peptides. The structure and pattern of synthesis of these peptides by leukocytes appear similar to neuroendocrine hormones, although some differences exist. Once secreted, these peptide hormones may function as endogenous regulators of the immune system as well as conveyors of information from the immune to the neuroendocrine system. The plasma hormone concentrations contributed by lymphocytes usually do not reach the levels required when the pituitary gland is the source, but because immune cells are mobile, they have the potential to locally deposit the hormone at the target site. Likewise, other studies show that cells of the neuroendocrine system contain receptors for cytokines and can also be considered a source of cytokines, particularly interleukin-1 (IL-1) and IL-6. In the pituitary IL-1 beta coexists with thyroid stimulating hormone in a subpopulation of thyrotropes, suggesting it may have a role as a pituitary paracrine factor. The cytokines, including IL-1, IL-2, IL-6, interferon-gamma, and tumor necrosis factor, exert profound effects on hypothalamic pituitary axes. It is our hypothesis that the relay of information to the neuroendocrine system represents a sensory function for the immune system wherein leukocytes recognize stimuli that are not recognizable by the central and peripheral nervous systems (i.e., bacteria, tumors, viruses, and antigens). The recognition of such noncognitive stimuli by immunocytes is then converted into information and a physiological change occurs. Future studies into the physiological role that cytokines and neuroendocrine hormones have in these systems will be of considerable interest for both immunologists and endocrinologists.

Animals↗

Phenobarbital specifically reduces gap junction protein mRNA level in rat liver.

The gene expression of liver major gap junction (GJ) protein was studied in rats systemically administered phenobarbital, a rat liver tumor promoter. Using a GJ protein cDNA and northern blot analysis, the level of GJ protein mRNA in liver was observed to be markedly reduced at 4 and 11 wk of phenobarbital exposure (0.1% in drinking water). However, the level of GJ protein mRNA was not altered in kidney at 11 wk of exposure. In liver, phenobarbital did not induce expression of the neoplasm-associated marker genes glutathione S-transferase (placental form) and gamma-glutamyltranspeptidase, while in kidney the observed expression of these genes was not changed. These in vivo results indicate that phenobarbital reduces GJ protein gene expression specifically in rat liver without altering expression of genes often altered during liver carcinogenesis, and they support assigning a role for the impairment of gap junctional intercellular communication in phenobarbital-mediated liver tumor promotion.

Animals↗

Tumor promotion: models and assay systems.

Tumor promotion is defined operationally from two-stage models of experimental carcinogenesis. It is, therefore, in a strict sense, possible to identify tumor promoters only from such models. The development and use of in vitro two-stage cell transformation assays was a logical extension toward in vitro short-term testing for tumor promoters. Another approach is to apply mechanistic knowledge of the tumor promotion process in developing end points for such assays. In this context, we have been examining the role of blocked gap-junctional intercellular communication (GJIC) in tumor promotion, using in vitro and in vivo systems. Many promoters have been shown to block GJIC in vitro; our studies support the idea that inhibition of GJIC does play an important role in the promotion stage of BALB/c 3T3 cell transformation. In animal studies, we have shown that the rat liver tumor promoter phenobarbital can decrease the level of expression of the 32 Kd gap junction protein gene specifically in liver upon systemic exposure in rats. Further examination of the role of GJIC in tumor promotion is indeed warranted. Also, deployment of in vitro GJIC and transformation assay systems should provide useful short-term tests for detecting tumor promoting activity of environmental chemicals.

Animals↗

Effects of calcium on the electric coupling of carotid body glomus cells.

Pairs of electrically coupled glomus cells from rat carotid bodies were impaled with microelectrodes. In the current clamp mode, intracellular stimulation and recording established the coupling coefficient (KC), across the intercellular junctions. About 80% of 26 pairs uncoupled during exposure to 9.45 mM [Ca2+]o, and about 72% of 18 pairs showed the same effect during applications of ionophore A23187. During superfusion with zero [Ca2+]o and EGTA, about 73% of 40 pairs of cells became more tightly coupled. Similar results (71%) were obtained during exposure of 42 cell pairs to BAPTA/AM, a membrane-permeant calcium chelator. Thus, [Ca2+]i seemed to play a significant a role in glomus cell intercellular communication. A23187 and BAPTA/AM, dissolved in DMSO, tended to reduce intercellular coupling during prolonged exposures of the preparations to this solvent. Consequently, the effects elicited by A23187 and BAPTA/AM were superimposed on a coupling effect produced by DMSO.

Animals↗

Listening in on bacteria: acyl-homoserine lactone signalling.

Bacterial cell-to-cell signalling has emerged as a new area in microbiology. Individual bacterial cells communicate with each other and co-ordinate group activities. Although a lot of detail is known about the mechanisms of a few well-characterized bacterial communication systems, other systems have been discovered only recently. Bacterial intercellular communication has become a target for the development of new anti-virulence drugs.

4-Butyrolactone↗

Gap junction formation during development of the mouse lens.

We have identified a 60 kDa membrane protein (MP60) as a component of the mouse cortical lens fiber gap junction and a monoclonal antibody recognizing this protein has been used to establish the temporal and spatial patterns of gap junction formation during development of the mouse lens. The initial expression of MP60 during embryonic development of the mouse lens correlates with primary fiber elongation and is first seen on the luminal aspect of the extending cells. About 2 days after birth, the relatively large, antibody-positive macular structures characteristic of late embryonic fiber cells begin to disperse into progressively smaller structures within a centrally located region of the lens. This change in the staining pattern with antibody directed against MP60 is consistent with the dispersion of gap junction plaques as confirmed by freeze fracture analysis. Around 5 days after birth, the 60 kDa gap junctional protein in this central region of the lens undergoes a modification resulting in the alteration to the epitope for the monoclonal antibody and a consequent loss of immunorecognition. Our results suggest that gap junctions in the central region of the developing mouse lens undergo sequential changes in immunoreactivity which may reflect potentially distinct functional phases of intercellular communication.

Age Factors↗

Hypoxia-reoxygenation inhibits gap junctional communication in cultured human umbilical vein endothelial cells.

We studied the change in gap junctional intercellular communication (GJIC) on human umbilical vein endothelial cells (HUVEC) under hypoxia-reoxygenation (H-R) conditions by the fluorescence redistribution after photobleaching (FRAP) method. Confluent HUVEC monolayers were exposed to hypoxia (pO2<0.1%) for 12 hours, and then were returned to normal atmospheric conditions for reoxygenation. Contrast microscopic observation showed no significant changes in the morphology of the HUVEC at any times after H-R. Reoxygenation following hypoxia caused time-dependent decrease in GJIC, that is, GJIC reduction was induced after 2 hours and reached maximum at 4-6 hours which recovered to normal levels after 18 hours. Oxidant sensitive fluorescence dye assay revealed that the generation of intracellular free radicals increased during the first 2 hours after reoxygenation. Hydroxyl radical scavengers (MCI-186, DMSO) and an iron chelator (deferoxamine) abolished the reduction of GJIC due to H-R. However, SOD, catalase and probucol were essentially inactive on this reduction. These data suggest that ischemia-reperfusion injury may be caused by a functional defect of GJIC induced by reactive oxygen radicals.

Antipyrine↗

Does transmembrane communication through gap junctions enable stem cells to overcome stromal inhibition?

When long-term bone marrow cultures are treated with Amphotericin B (AB) their haemopoietic stem cells (HSC) cease growing. This is not a toxic effect of the drug because once that is removed, HSC resume clonal growth and, given sufficient time, form as many cells as HSC in untreated cultures. Amphotericin B-evoked inhibition of blood formation is probably mediated by transmembrane communication between HSC and stroma for the following reasons: (1) AB does not stop HSC forming colony-forming units in culture (CFU-c) when HSC are separated from stroma by culturing them on Transwell inserts above the stroma. (2) Conditioned media (CM) from AB-containing or normal long-term cultures (LTC) does not inhibit normal marrow cells forming colonies in semi-solid cultures without stromal underlays. (3) AB itself does not stop bone marrow cells forming colonies in semi-solid cultures nor does it stop stromal cells growing or prejudice their long-term maintenance. (4) Furthermore, growing stromal cells with AB does not alter the number of transcripts they form for cytokines and chemokines to any large extent, including TGF-beta1. We have extensive, though circumstantial, evidence that gap junctions are involved in this communication. AB only stopped the growth of HSC when we blocked intercellular communication via gap junctions (GJIC) (tested by micro-injection of lucifer yellow). Lipophilic compounds that do not affect GJIC had no effect on the growth of HSC. Looking at a series of stromal cell lines from foetal liver and neonatal bone marrow we found that extensive GJIC correlated with stromal support of the late-appearing clones formed by primitive HSC (week 3-5 cobblestone-area forming cells, CAFC). We propose that the proliferation of HSC is regulated via transmembrane communication between stromal and HSC. Our findings support the proposal that gap junctions play a part in this stromal-dependent regulation.

Amphotericin B↗

Localization and possible role of molecules associated with the cholinergic system during "non-nervous" developmental events.

Data on the non-nervous location of cholinergic molecules are reviewed to give a general indication of their possible functions. Cholinergic or immunologically related molecules were detected and localized mainly in three classes of differentiative events supported by intracellular ion concentration changes. I: during gamete maturation, activation and interaction; II: during the early development of invertebrate and vertebrate embryos. In this case cholinergic molecules are located mainly in moving cells and tissues engaged in relevant morphogenetic events, such as gastrulation and limb bud differentiation, and are often codistributed with special extracellular matrix molecules (fibronectin); III: during inductive communications between mesenchyme and other tissues. The cholinergic system thus seems to be a multifunctional cell communication system. It appeared early during evolution as a regulator of intercellular communications mediated by ion dynamics, before becoming involved in highly specialized communication structures, such as synapses and nerve endings.

Animals↗

Regulation of cell-to-cell communication in non-tumorigenic and malignant human prostate epithelial cells.

BACKGROUND: Gap-junction-mediated intercellular communication (GJIC) is required for normal development and tissue homeostasis. However, the role of GJIC in human prostate carcinogenesis and progression remains ill-defined. METHODS: The ability of hormones, anti-hormones, and the anti-hypertensive drug, forskolin, to restore GJIC in non-tumorigenic (RWPE-1 and PWR-1E) and malignant (RWPE-2, LNCaP, DU-145) human prostate epithelial cell lines, was examined by Scrape-Loading/Dye Transfer (SL/DT) and Fluorescence Recovery After Photobleaching (FRAP) methods using an Ultima laser cytometer. RESULTS: Results from both assays show that PWR-1E, RWPE-2, LNCaP, and DU-145 cells have weak or absent GJIC activity. However, the non-tumorigenic RWPE-1 cells showed restoration of some GJIC (nearly 10%) after 1 hr in the FRAP assay. Forskolin and estrone, which increase intracellular cAMP levels, induced a significant and consistent increase (2.8- and 4.4-fold, respectively) in cell-to-cell communication only in the non-tumorigenic RWPE-1 cells. Furthermore, estrone induced a two-fold increase in connexin 43 (Cx43) and a 30% decrease in Cx32 expression, while forskolin caused a 50% reduction in Cx32 with no effect on Cx43 expression in RWPE-1 cells. CONCLUSIONS: These data suggest that agents that increase Cx43:Cx32 ratio may be used to restore GJIC in junctionally-deficient, non-tumorigenic immortalized cells, thus providing insights into potential mechanisms responsible for the multistep carcinogenesis in the human prostate.

Cell Communication↗

Reduced junctional permeability at interrhombomeric boundaries.

Intercellular communication is considered to have a role during pattern specification processes in early embryonic development. This report analyzes the changing gap junctional communication properties of chick neuroepithelial cells depending on their position relative to the segmental partitions of the rhombencephalon. Intercellular electrical coupling and dye transfer were studied with microelectrode techniques. Neuroepithelial cells were electrically coupled irrespective of their location relative to interneuromeric boundaries. Iontophoretic injection of biocytin or Lucifer Yellow into single cells inside the rhombomeres was followed by transjunctional diffusion to the surrounding cells. In contrast, dye transfer was strictly limited when the diffusion zone contacted the cells forming the interneuromeric limits. Label injected into the boundary cells did not spread to other cells at all. Avian interrhombomeric boundaries are thus sites of reduced junctional permeability during early morphogenesis.

Animals↗