Cell Communication Mechanisms Research Articles

Oregano essential oil-pectin edible films as anti-quorum sensing and food antimicrobial agents.

Edible films can be used as carriers for antimicrobial compounds to assure food safety and quality; in addition, pathogenesis of food bacteria is related to a cell to cell communication mechanism called quorum sensing (QS). Oregano essential oil (OEO) has proved to be useful as food antimicrobial; however, its food applications can be compromised by the volatile character of its active constituents. Therefore, formulation of edible films containing OEO can be an alternative to improve its food usages. QS inhibitory activity of OEO and pectin-OEO films was evaluated using Chromobacterium violaceum as bacterial model. Additionally, antibacterial activity was tested against Escherichia coli O157:H7, Salmonella Choleraesuis, Staphylococcus aureus, and Listeria monocytogenes. OEO was effective to inhibit bacterial growth at MIC of 0.24 mg/mL for all tested bacteria and MBC of 0.24, 0.24, 0.48, and 0.24 mg/mL against E. coli O157:H7, S. Choleraesuis, S. aureus, and L. monocytogenes, respectively. Pectin-films incorporated with 36.1 and 25.9 mg/mL of OEO showed inhibition diameters of 16.3 and 15.2 mm for E. coli O157:H7; 18.1 and 24.2 mm for S. Choleraesuis; 20.8 and 20.3 mm for S. aureus; 21.3 and 19.3 mm for L. monocytogenes, respectively. Pectin-OEO film (15.7 mg/mL) was effective against E. coli O157:H7 (9.3 mm), S. aureus (9.7 mm), and L. monocytogenes (9.2 mm), but not for S. Choleraesuis. All concentrations of OEO (0.0156, 0.0312, 0.0625 and 0.125 mg/mL) and pectin-OEO films (15.7, 25.9 and 36.1 mg/mL) showed a significant anti-QS activity expressed as inhibition of violacein production by C. violaceum. Additionally, the application of pectin-OEO films was effective reducing total coliforms, yeast, and molds of shrimp and cucumber slices stored at 4°C during 15 d. These results demonstrated the potential of pectin films enriched with OEO as food related microorganisms and QS inhibitors.

FRI0348 Microparticles in Rheumatoid Arthritis Patients: A Principal Component Analysis Approach

BackgroundMicroparticles (MP) come from cell activation and apoptosis. Largely considered as cell waste and debris, now it is known they could represent a mechanism of cell communication. Circulating MP have...

Trogocytosis in allogeneic transplants

Trogocytosis has been identified as a mechanism of cell communication between immune cells. Unlike the more common receptor-ligand signaling, trogocytosis results in the transfer of intact and functional surface proteins between cells. For example, antigen presenting cells in contact with T cells exchange proteins which results in the T-cell acquiring antigen presentation capabilities. This allows for the newly activated T cells to stimulate other T cells thus amplifying the immune response. We have recently demonstrated that during allogeneic hematopoietic stem cell transplantation the donor cells obtain recipient MHC class I proteins by trogocytosis. The effect is a donor cell that can masquerade as a recipient cells and evade detection by NK cells and macrophages.

Evolutionary biology redux.

This article offers a novel, enlightened concept for determining the mechanism of evolution. It is based on homeostasis, which distinguishes life from non-life and as such is the universal mechanism for the evolution of all living organisms. This view of evolution is logical, mechanistic, non-scalar, predictive, testable, and falsifiable, and it illuminates the epistemological relationships between physics and biology, ontogeny and phylogeny, development and aging, ultimate and proximate causation, health and disease. In addition to validating Haeckel's biogenetic law and Lamarckian epigenetics, reflecting the enabling value of the cellular approach, this perspective also expresses the evolutionary process at the cell-molecular level, since the mechanism of cell communication itself is universal in biology, in keeping with a Kuhnian paradigm shift. This approach may even elucidate the nature and evolution of consciousness as a manifestation of the cellular continuum from unicellular to multicellular life. We need such a functional genomic mechanism for the process of evolution if we are to make progress in biology and medicine. Like Copernican heliocentrism, a cellular approach to evolution may fundamentally change humankind's perceptions about our place in the universe.

Extracellular vesicles in chronic lymphocytic leukemia

Extracellular vesicles (EVs) are membrane-enclosed nanoparticles 30 to 1000 nm in size and represent a novel mechanism of cell communication. By transferring RNA and protein from their cell of origin, they can reprogram target cells and thus are involved in changes within the cellular microenvironment – a key player in CLL pathogenesis. In the current study, we were able to isolate EVs of 20 to 300 nm from blood plasma of CLL patients as well as from supernatant of primary CLL cells in culture. Further, proteomic profiling by Coomassie staining of SDS-PAGE gels and by mass spectrometry revealed an EV-specific protein profile. These findings suggest that EVs represent an important mean of CLL cells to interact with other cells, which might contribute to the establishment of a pro-survival microenvironment for CLL cells.

Antipathogenic potential of Rhizophora spp. against the quorum sensing mediated virulence factors production in drug resistant Pseudomonas aeruginosa

Quorum sensing (QS) is a process of cell–cell communication mechanism occurs between the bacterial cells through the secretary signal molecules. This QS mechanism has been shown to control over the expression of various genes responsible for the production of virulence factors in several bacterial pathogens. Hence, the present study was intended to evaluate the antipathogenic potential of mangrove trees of the genus Rhizophora against the QS dependent virulence factors production in Pseudomonas aeruginosa PAO1, clinical isolates CI-I (GU447237) and CI-II (GU447238). The methanol extract of Rhizophora apiculata and R. mucronata (1mg/ml) showed significant inhibition against QS dependent virulence factors production such as LasA protease, LasB elastase, total protease, pyocyanin pigment production and biofilm formation in P. aeruginosa PAO1, CI-I and CI-II. This study for the first time, reports the quorum sensing inhibitory (QSI) potential of Rhizophora spp. against P. aeruginosa infections.

Abstract 1528: Tunneling Nanotubes: a new approach to studying intercellular communication in aggressive solid tumor malignancies.

Abstract Background: Intercellular communication is critical to malignant progression, invasion, and recurrence, yet surprisingly little is known about the mechanisms of cell-cell communication in the complex heterogeneous tumor microenvironment. Tunneling nanotubes (TnTs) are long, non-adherent, actin-based cellular extensions that act as short and long-range conduits for transport of cellular cargo between connected cells. We have studied these unique structures in mesothelioma and lung cancer, and further confirmed that they can form and connect cells derived from cell lines and also from primary human cells from cancers of the breast, ovary, cervix, prostate, pancreas, bone (osteosarcoma), and brain (glioblastoma), indicating that nanotubes are a potential mechanism of cell communication across cancer types. We have previously demonstrated that TnTs are present in tumor specimens resected from human patients with malignant pleural mesothelioma and lung adenocarcinomas, and that they can mediate transport of mitochondria, proteins, and Golgi vesicles between connected cells. Time-lapse confocal microscopy demonstrated that TnTs can form de novo between mesothelioma cells over several hours. Exosomes - small membrane-derived nanovesicles measuring 30-100 nm in diameter - are also under extensive investigation as critical signals for communication and cell growth in cancer. We hypothesized that co-culturing exosomes with mesothelioma cells would provide a chemotactic stimulus for TnT formation. Cholesterol accumulation has been proposed to have a direct effect on TnTs; cholesterol-based microdomains known as lipid rafts have been associated with exosome signaling as well. In the current study, we also explored lipid raft expression in the context of TnTs in mesothelioma. Results: We examined whether addition of exogenous exosomes induced increased formation of tunneling nanotubes. Mesothelioma cells co-cultured in vitro with exogenous exosomes formed more TnTs than cells cultured without exosomes by 48 hours. Average number of nanotubes was higher when exosomes were co-cultured in acidic conditions as compared to non-acidic culture conditions, but this was only statistically significant within the first 24 hours. Electron microscopy revealed that exosomes were located at the base of and co-localized with TnTs, as well as being present in the extracellular environment. Mesothelioma cells connected via nanotubes were enriched with lipid rafts. Conclusions: Our findings implicate exosomes as potential chemotactic stimuli for tunneling nanotube formation. Future studies will further examine the role of lipid rafts in TnT formation and function. Citation Format: Emil Lou, Victor Babatunde, Sho Fujisawa, Afsar Barlas, Andre L. Moreira, Venugopal Thayanithy, Subbaya Subramanian, Robert Downey, Katia Manova-Todorova, Malcolm A.S. Moore. Tunneling Nanotubes: a new approach to studying intercellular communication in aggressive solid tumor malignancies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1528. doi:10.1158/1538-7445.AM2013-1528

Abstract TP265: Microparticles Play A Role In Mediating Angiogenic Effect Of Mesenchymal Stromal Cells On Cerebral Vascular Endothelial Cells

Microparticles (MPs) represent a novel network for intercellular communication. Our previous works found that MPs from db/db diabetic mice impaired endothelial progenitor cell function. This study investigated the role of MPs from mesenchymal stromal cells (MSCs) in regulating cerebrovascular endothelial cell (cEC) function and gene expression. Male C57BL/6 mice and green fluorescent protein (GFP)-transgenic mice were used for cEC and MSC donors, respectively. The cECs were cultured on 6-well plates and MSCs were seeded on well inserts with a 0.4 μm pore sized filter for co-culture for 3 days before various measurements. MSC conditional medium (MSC-CM) was used for producing MPs and MSC-CM deprived of MPs (MSC-CM-dMP) by centrifuge. MPs deprived of mRNAs and miRNAs (MSC-MP-dRNA) were prepared by treating with RNAse. In some experiments, cECs were incubated with normal culture medium (control), MSC-CM, MSC-CM-dMP, MSC-MPs or MSC-MP-dRNA for 3 days. After different treatments, the cECs were used for confocal microscopy analysis of GFP level, real-time PCR analysis of angiogenic gene expression and functional analyses. The levels of angiogenic factors were measured by ELISA method. Results showed: 1) GFP-MPs were appeared in cEC culture medium, and GFP was detected in cECs after co-culture with MSCs; 2) Co-culture with MSCs or culture with MSC-CM significantly upregulated mRNA expression of VEGFR2 and CXCR4 in cECs and increased the angiogenic factors (VEGF and SDF-1) in culture supernatant; 3) Co-culture with MSCs or culture with MSC-CM increased cEC function (migration: 68.6 ± 3.2, 66.8 ± 2.6 and 48.8 ± 2.6 tubes/field for MSC, MSC-CM and control, respectively; tube formation: 52.8 ± 2.6, 48.8 ± 2.0 and 32.6 ± 1.2 tubes/field for MSC, MSC-CM and control, respectively; n=5/group, P <0.05 or 0.01, vs. control); 4) Whereas, incubation with MSC-CM-dMP or MSC-MP-dRNA aborted the effect on mRNA expression, and reduced the functional effects by about 50%. In conclusion, MPs mediate angiogenic effect of MSCs on cECs via RNA and/or protein deliveries, which represent a novel mechanism of cell communication, providing a potential therapeutic target for endothelial dysfunction and cerebrovascular diseases.

Notch1-mediated signaling regulates proliferation of porcine satellite cells (PSCs)

Notch signaling is an evolutionarily conserved cell–cell communication mechanism involved in the regulation of cell proliferation, differentiation and fate decisions of mammalian cells. In the present study, we investigated the possible requirement for Notch signaling in the proliferation and differentiation of porcine satellite cells. We show that Notch1, 2 and 3 are expressed in cultured porcine satellite cells. Knock-down of NOTCH1, but not NOTCH2 and NOTCH3, decreases the proliferation of porcine satellite cells. In contrast, enhancement of NOTCH1 expression via treatment of porcine satellite cells with recombinant NF-κB increases the proliferation of porcine satellite cells. The alteration of porcine satellite cell proliferation is associated with significant changes in the expression of cell cycle related genes (cyclin B1, D1, D2, E1 and p21), myogenic regulatory factors (MyoD and myogenin) and the Notch effector Hes5. In addition, alteration of Notch1 expression in porcine satellite cells causes changes in the expression of GSK3β-3. Taken together, these findings suggest that of the four notch-related genes, Notch1is likely to be required for regulating the proliferation and therefore the maintenance of porcine satellite cells in vivo, and do so through activation of the Notch effector gene Hes5.

Abstract 6: Therapeutic Angiogenesis by Human CD34+ Hematopoietic Stem Cells via Exosomes-Mediated MicroRNA Transfer

Introduction: Locally transplanted human CD34+ hematopoietic stem cells have stimulated neovascularization in preclinical studies and have been associated with functional improvements in phase I and II clinical trials of patients with ischemic cardiovascular diseases. Recently, we have demonstrated that membrane-bound nano-vesicles called exosomes are one of the primary pro-angiogenic components of human CD34+ cell paracrine secretion that induced angiogenesis independently of the cells. Here, we hypothesize that the functional benefits associated with CD34+ cell therapy are primarily mediated by the secretion of exosomes (Exo), and that CD34+ Exo transfer pro-angiogenic microRNAs to promote angiogenesis and ischemic tissue repair. Methods and Results: Therapeutic potential of CD34+ Exo isolated from adult human peripheral blood-derived CD34+ cells was evaluated in a mouse model of hind limb ischemia (HLI). Similar to CD34+ cells, administration of CD34+ Exo from equal number of cells induced angiogenesis and tissue repair; it significantly improved perfusion (ratio: 1.01±0.04 v 0.57±0.1, P<0.05), increased capillary density (1.8±0.3/HPF v 0.9±0.1/HPF, p<0.001) and prevented ischemic leg amputation (16% v 100%), compared to Exo from non-angiogenic, CD34+ cell-depleted-mononuclear cells (MNC Exo). Our microarray data and confirmatory tests revealed that unlike MNC Exo, CD34+ Exo are enriched in pro-angiogenic miRNAs such as miR-126. Flow cytometry and live confocal imaging demonstrated that Cy3-tagged miRNA in CD34+ Exo is directly transferred to endothelial cells in vitro and in ischemic tissues in vivo; concurrent loss of function gain of function studies prove that direct transfer of miR-126 is crucial for CD34+ Exo-induced angiogenesis and functional recovery. To address whether exosome secretion is needed for miR-126 transfer, we are exploring the effect of inhibition of exosome secretion from CD34+ cells. Conclusion: CD34+ exosomes transfer the pro-angiogenic miR-126 to endothelial cells in the ischemic tissues to induce angiogenesis and ischemic tissue repair. Our study illustrates a mechanism of stem cell communication involving intercellular traffic of miRNAs via exosomes to induce functional recovery.

Effect of Alpha 2 Macroglobulin on Luteal Cell Induced Gamma Delta T Lymphocyte Proliferation.

The paracrine factors that regulate communication between immune cells and parenchymal cells within the corpus luteum (CL) are not well defined. It has been shown that cultured luteal cells are profound stimulators of T lymphocytes and can induce T cell proliferation by cell to cell interactions and by secretory factors. By using a proteomic approach, we profiled protein expression in conditioned media from gamma delta T cell - luteal cell (LC) cocultures collected from midcycle and regressing CL. Alpha 2 macroglobulin (a2M) was one of the proteins that exhibited differential secretion. The purpose of this study was to determine if a2M mediates LC induced changes in gamma delta T cell function in fully functional, but not regressing CL. The first objective was to define if a2M secretion can be modified by luteolytic factors. Midcycle luteal cells were exposed to transforming growth factor beta(TGFb), interferon gamma/ tumor necrosis factor (IFNg/TNFa) and PGF2a. Luteal conditioned media (LCM) were collected on days 1 and 3 of cultures and protein expression was analyzed by Western Blot. Although PGF2a reduced a2M secretion in both days of collection, the effect of IFNg/TNFa was observed only on day 3 (p<0.05). The second objective was to determine if a2M mediates gamma delta T cells proliferation in response to luteal cells depending on functional status of the CL. Corpora lutea were collected from cyclic cattle on days 10–12 of the estrous cycle and 8hrs after PGF2a injection, dissociated and placed in culture. To test two different ways of cells communication, immunomagnetically isolated gamma delta T cells from the blood were placed in culture with luteal cells in contact or inside a culture insert. Cells were than incubated for 72hrs with or without a2M and proliferation of gamma delta T cells was measured. In cells collected from regressing CL, a2M increased LC stimulated gamma delta T cells proliferation only when the cells were physically separated by insert. The gamma delta T cells response to midcycle LC was not altered by a2M. The third objective was to examine if a2M can induce gamma delta T cells proliferation directly. The luteal cells were first fixed with 0.1% and 1% paraformaldehyde. Gamma delta T cells and a2M were then added to the culture system and a proliferation assay was performed after 72 hrs. This study showed that cell fixation reduced gamma delta T cells response to LC respectively to 40% and 23%. Treatment with a2M had no effect on gamma delta T cell proliferation. In conclusion, we showed that a2M protein expression varied within the estrous cycle and was regulated by factors locally secreted in the CL. The role of a2M is to entrap and bind diverse molecules secreted by luteal cells and facilitate their delivery to immune cells. Our data suggests that proteins like a2M may provide an alternative mechanism for cell communication in tissues undergoing rapid morphological changes to maintain local homeostasis. This project was supported by National Research Initiative Competitive Grant no. 2008-35203-04617 from the USDA National Institute of Food and Agriculture.

Genes encoding heterotrimeric G-proteins are associated with gray matter volume variations in the medial frontal cortex.

G-protein–coupled signal transduction mediates most cellular responses to hormones and neurotransmitters; this signaling system transduces a large variety of extracellular stimuli into neurons and is the most widely used mechanism for cell communication at the synaptic level. The heterotrimeric G-proteins have been well established as key regulators of neuronal growth, differentiation, and function. More recently, the heterotrimeric G-protein genes group was associated with general cognitive ability. Although heterotrimeric G-proteins are linked to both cognitive ability aond neuron signaling, it is unknown whether heterotrimeric G-proteins are also important for brain structure. We tested for association between local cerebral gray matter volume and the heterotrimeric G-protein genes group in 294 subjects; a replication analysis was performed in an independent sample of 238 subjects. Voxel-based morphometry revealed a strong replicated association between 2 genes encoding heterotrimeric G-proteins with specific local increase in medial frontal cortex volume, an area known to be involved in cognitive control and negative affect. This finding suggests that heterotrimeric G-proteins might modulate medial frontal cortex gray matter volume. The differences in gray matter volume due to variations in genes encoding G-proteins may be explained by the role of G-proteins in prenatal and postnatal neocortex development.

Detection, Characterization, and Biological Effect of Quorum-Sensing Signaling Molecules in Peanut-Nodulating Bradyrhizobia

Bacteria of the genus Bradyrhizobium are able to establish a symbiotic relationship with peanut (Arachis hypogaea) root cells and to fix atmospheric nitrogen by converting it to nitrogenous compounds. Quorum sensing (QS) is a cell-cell communication mechanism employed by a variety of bacterial species to coordinate behavior at a community level through regulation of gene expression. The QS process depends on bacterial production of various signaling molecules, among which the N-acylhomoserine lactones (AHLs) are most commonly used by Gram-negative bacteria. Some previous reports have shown the production of QS signaling molecules by various rhizobia, but little is known regarding mechanisms of communication among peanut-nodulating strains. The aims of this study were to identify and characterize QS signals produced by peanut-nodulating bradyrhizobial strains and to evaluate their effects on processes related to cell interaction. Detection of AHLs in 53 rhizobial strains was performed using the biosensor strains Agrobacterium tumefaciens NTL4 (pZLR4) and Chromobacterium violaceum CV026 for AHLs with long and short acyl chains, respectively. None of the strains screened were found to produce AHLs with short acyl chains, but 14 strains produced AHLs with long acyl chains. These 14 AHL-producing strains were further studied by quantification of β-galactosidase activity levels (AHL-like inducer activity) in NTL4 (pZLR4). Strains displaying moderate to high levels of AHL-like inducer activity were subjected to chemical identification of signaling molecules by high-performance liquid chromatography coupled to mass spectrometry (LC-MS/MS). For each AHL-producing strain, we found at least four different AHLs, corresponding to N-hexanoyl-dl-homoserine lactone (C6), N-(3-oxodecanoyl)-l-homoserine lactone (3OC10), N-(3-oxododecanoyl)-l-homoserine lactone (3OC12), and N-(3-oxotetradecanoyl)-l-homoserine lactone (3OC14). Biological roles of 3OC10, 3OC12, and 3OC14 AHLs were evaluated in both AHL-producing and -non-producing peanut-nodulating strains. Bacterial processes related to survival and nodulation, including motility, biofilm formation, and cell aggregation, were affected or modified by the exogenous addition of increasing concentrations of synthetic AHLs. Our results clearly demonstrate the existence of cell communication mechanisms among bradyrhizobial strains symbiotic of peanut. AHLs with long acyl chains appear to be signaling molecules regulating important QS physiological processes in these bacteria.

Signalling mechanisms of RhoGTPase regulation by the heterotrimeric G proteins G12 and G13

G protein-mediated signal transduction can transduce signals from a large variety of extracellular stimuli into cells and is the most widely used mechanism for cell communication at the membrane. The RhoGTPase family has been well established as key regulators of cell growth, differentiation and cell shape changes. Among G protein-mediated signal transduction, G12/13-mediated signalling is one mechanism to regulate RhoGTPase activity in response to extracellular stimuli. The alpha subunits of G12 or G13 have been shown to interact with members of the RH domain containing guanine nucleotide exchange factors for Rho (RH-RhoGEF) family of proteins to directly connect G protein-mediated signalling and RhoGTPase signalling. The G12/13-RH-RhoGEF signalling mechanism is well conserved over species and is involved in critical steps for cell physiology and disease conditions, including embryonic development, oncogenesis and cancer metastasis. In this review, we will summarize current progress on this important signalling mechanism.

NMDA Receptor Contributions to Visual Contrast Coding

In the retina, it is not well understood how visual processing depends on AMPA- and NMDA-type glutamate receptors. Here we investigated how these receptors contribute to contrast coding in identified guinea pig ganglion cell types in vitro. NMDA-mediated responses were negligible in ON alpha cells but substantial in OFF alpha and delta cells. OFF delta cell NMDA receptors were composed of GluN2B subunits. Using a novel deconvolution method, we determined the individual contributions of AMPA, NMDA, and inhibitory currents to light responses of each cell type. OFF alpha and delta cells used NMDA receptors for encoding either the full contrast range (alpha), including near-threshold responses, or only a high range (delta). However, contrast sensitivity depended substantially on NMDA receptors only in OFF alpha cells. NMDA receptors contribute to visual contrast coding in a cell-type-specific manner. Certain cell types generate excitatory responses using primarily AMPA receptors or disinhibition.

Analytical approaches to investigate transmitter content and release from single secretory vesicles

The vesicle serves as the primary intracellular unit for the highly efficient storage and release of chemical messengers triggered during signaling processes in the nervous system. This review highlights conventional and emerging analytical methods that have used microscopy, electrochemistry, and spectroscopy to resolve the location, time course, and quantal content characteristics of neurotransmitter release. Particular focus is on the investigation of the synaptic vesicle and its involvement in the fundamental molecular mechanisms of cell communication.

Synchronized Network Oscillations in Rat Tuberoinfundibular Dopamine Neurons: Switch to Tonic Discharge by Thyrotropin-Releasing Hormone

The pituitary hormone, prolactin, triggers lactation in nursing mothers. Under nonlactating conditions, prolactin secretion is suppressed by powerful inhibition from hypothalamic tuberoinfundibular dopamine (TIDA) neurons. Although firing pattern has been suggested as integral to neuroendocrine control, the electrical behavior of TIDA cells remains unknown. We demonstrate that rat TIDA neurons discharge rhythmically in a robust 0.05 Hz oscillation. The oscillation is phase locked between neurons, and while it persists during chemical synaptic transmission blockade, it is abolished by gap junction antagonists. Thyrotropin-releasing hormone (TRH) potently stimulates prolactin release, an effect assumed to take place in the pituitary. In TIDA cells, TRH caused a transition from phasic to tonic firing through combined pre- and postsynaptic effects. These findings suggest a model for prolactin regulation where a TIDA network switch from oscillations to sustained discharge converts dopamine from an antagonist at high concentrations to a functional agonist as dopamine output from the network decreases.

Two novel neuropeptides in innervation of the salivary glands of the black‐legged tick, Ixodes scapularis: Myoinhibitory peptide and SIFamide

AbstractThe peptidergic signaling system is an ancient cell–cell communication mechanism that is involved in numerous behavioral and physiological events in multicellular organisms. We identified two novel neuropeptides in the neuronal projections innervating the salivary glands of the black‐legged tick, Ixodes scapularis (Say, 1821). Myoinhibitory peptide (MIP) and SIFamide immunoreactivities were colocalized in the protocerebral cells and their projections terminating on specific cells of salivary gland acini (types II and III). Immunoreactive substances were identified by matrix‐assisted laser desorption/ionization‐time of flight (MALDI‐TOF) analysis: a 1,321.6‐Da peptide with the sequence typical for MIP (ASDWNRLSGMWamide) and a 1,395.7‐Da SIFamide (AYRKPPFNGSIFamide), which are highly conserved among arthropods. Genes encoding these peptides were identified in the available Ixodes genome and expressed sequence tag (EST) database. In addition, the cDNA encoding the MIP prepropeptide was isolated by rapid amplification of cDNA ends (RACE). In this report, we describe the anatomical structure of specific central neurons innervating salivary gland acini and identify different neuropeptides and their precursors expressed by these neurons. Our data provide evidence for neural control of salivary gland by MIP and SIFamide from the synganglion, thus lending a basis for functional studies of these two distinct classes of neuropeptides. J. Comp. Neurol. 517:551–563, 2009. © 2009 Wiley‐Liss, Inc.

Immune and Nervous Systems: More Than Just a Superficial Similarity?

Strong evidence is emerging that the nervous and immune systems share mechanisms of gene regulation, signaling, cell communication, and supracellular organization. This brings to the fore many questions, not least of which is the developmental and evolutionary origin of the commonalities between the two systems. By providing answers to these questions, immunologists and neurobiologists increasingly expose the mechanistic and conceptual affinities of their respective fields and facilitate the understanding of fundamental principles that govern the organization of complex cellular systems. The current essay and reviews in Immunity and Neuron attempt to communicate to the wider scientific community a series of examples relating to commonalities between the immune and nervous system and enhance the dialog and exchange of ideas between the two fields.

Two novel neuropeptides in innervation of the salivary glands of the black‐legged tick, Ixodes scapularis: Myoinhibitory peptide and SIFamide

AbstractThe peptidergic signaling system is an ancient cell–cell communication mechanism that is involved in numerous behavioral and physiological events in multicellular organisms. We identified two novel neuropeptides in the neuronal projections innervating the salivary glands of the black‐legged tick, Ixodes scapularis (Say, 1821). Myoinhibitory peptide (MIP) and SIFamide immunoreactivities were colocalized in the protocerebral cells and their projections terminating on specific cells of salivary gland acini (types II and III). Immunoreactive substances were identified by matrix‐assisted laser desorption/ionization‐time of flight (MALDI‐TOF) analysis: a 1,321.6‐Da peptide with the sequence typical for MIP (ASDWNRLSGMWamide) and a 1,395.7‐Da SIFamide (AYRKPPFNGSIFamide), which are highly conserved among arthropods. Genes encoding these peptides were identified in the available Ixodes genome and expressed sequence tag (EST) database. In addition, the cDNA encoding the MIP prepropeptide was isolated by rapid amplification of cDNA ends (RACE). In this report, we describe the anatomical structure of specific central neurons innervating salivary gland acini and identify different neuropeptides and their precursors expressed by these neurons. Our data provide evidence for neural control of salivary gland by MIP and SIFamide from the synganglion, thus lending a basis for functional studies of these two distinct classes of neuropeptides. J. Comp. Neurol. 517:551–563, 2009. © 2009 Wiley‐Liss, Inc.