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Neuro-immune modulation in the gastrointestinal tract


Principle investigator: Alfons Kroese, Ph.D.
Project description:
The aim of the project is the morphological, electrophysiological and neuropharmacological identification of the role, the mechanisms and the effects of the bi-directional interactions between the enteric nervous system and the enteric immune system on the functioning of the gastrointestinal tract under normal and inflammatory conditions.
Cellular electrophysiology and neuropharmacology using sharp and patch clamp microelectrode techniques for studying voltage-gated and ligand-gated ion channels and the excitability of neurons. Confocal laser scanning microscopy using fluorescent dyes for measurement of intracellular Ca2+ concentration. Immunohistochemistry with antibodies for identification of membrane receptors and cellular neuropeptides. Enteric neurons in wholemount preparations, cultured neurons, cell lines and primary cultured mast cells. Quantification of the integrity and permeability of the intestinal barrier in vitro in Ussing chambers.
Mast cells are often found in close proximity of sensory nerve endings in the intestine and there is a direct bi-directional communication between mast cells and the neurons. Intestinal inflammation has consequences for the functioning of the enteric nervous system, especially resulting from the activation of neurons by inflam­ma­tory media­tors such as prostaglandi­nes and interleukins. Alterations in this regulatory process, so as for instance occur during acute pancreatitis, food allergy and intoxication, can induce changes in permeability and integrity of the intestinal barrier.
- Rijnierse, A., Kraneveld, A.D., Salemi, A., Zwaneveld, S., Goumans, A.P., Rychter, J.W., Thio, M., Redegeld, F.A., Westerink, R.H.S., Kroese, A.B.A. (2013). Immunoglobulinfree light chains reduce in an antigen-specific manner the rate of rise of action potentials of mouse non-nociceptive dorsal root ganglion neurons. Journal of Neuroimmunology 264, 14-23.
- Bagyánszki, M., Torfs, P., Krecsmarik, M., Fekete, E., Adriaensen, D., Van Nassauw, L., Timmermans, J.P., Kroese, A.B.A. (2011). Chronic alcohol consumption induces an overproduction of NO by nNOS- and iNOS-expressing myenteric neurons in the murine small intestine. Neurogastroenterology and Motility 23, e237-248. 
- Rychter, J.W., Van Nassauw, L., Timmermans, J.P., Akkermans, L.M.A., Westerink, R.H.S., Kroese, A.B.A. (2011). CGRP1 receptor activation induces piecemeal release of protease-1 from mouse bone marrow-derived mucosal mast cells. Neurogastroenterology and Motility 23, e57-68.
- Bagyánszki, M., Krecsmarik, M., De Winter, B.Y., De Man, J.G., Fekete, E., Pelckmans, P.A., Adriaensen, D., Kroese, A.B., Nassauw, L.V., Timmermans, J.P. (2010). Chronic alcohol consumption affects gastrointestinal motility and reduces the proportion of neuronal NOS-immunoreactive myenteric neurons in the murine jejunum. Anatomical Record  293, 1536-1542.
- Heusinkveld, H.J., Thomas, G.O., Lamot, I., van den Berg, M., Kroese, A.B.A., & Westerink, R.H.S. (2010). Dual actions of lindane (γ-hexachlorocyclohexane) on calcium homeostasis and exocytosis in rat PC12 cells. Toxicology and Applied Pharmacology  248, 12-19.
- Rychter, J.W., Van Nassauw, L., Brown, J.K., Van Marck, E., Knight, P.A., Miller, H.R.P., Kroese, A.B.A., Timmermans, J-P. (2010) Impairment of intestinal barrier and secretory function as well as egg excretion during intestinal schistosomiasis occur independently of mouse mast cell protease-1. Parasite Immunology; 32, 221-231.
- de With, M.C., de Vries, A.M., Kroese, A.B., van der Heijden, E.P., Bleys, R.L., Segal, S.S., Kon, M. (2009). Vascular anatomy of the hamster retractor muscle with regard to its microvascular transfer. European surgical research 42, 97-105.
- de With, M.C., van der Heijden, E.P., van Oosterhout, M.F., Kon, M., Kroese, A.B. (2009). Contractile and morphological properties of hamster retractor muscle following 16 h of cold preservation. Cryobiology 59, 308-316.
- Rijnierse, A., Kroese, A.B., Redegeld, F.A., Blokhuis, B.R., van der Heijden, M.W., Koster, A.S., Timmermans, J.P., Nijkamp, F.P., Kraneveld, A.D. (2009). Immunoglobulin-free light chains mediate antigen-specific responses of murine dorsal root ganglion neurons. Journal of Neuroimmunology 208, 80-86.
- Rychter, J.W., van Minnen, L.P., Verheem, A., Timmerman, H.M., Rijkers, G.T., Schipper, M.E.I., Gooszen, H.G., Akkermans, L.M.A., Kroese, A.B.A. (2009). Pretreatment but not treatment with probiotics abolishes mouse intestinal barrier dysfunction in acute pancreatitis. Surgery 145, 157-167.
- De Proost, I., Pintelon, I., Brouns, I., Kroese, A.B., Riccardi, D., Kemp, P.J., Timmermans, J.P., Adriaensen, D. (2008). Functional live cell imaging of the pulmonary neuroepithelial body microenvironment. American Journal of Respiratory Cell and Molecular Biology 39, 180-189.
- Venneman, N.G., Petruzzelli, M., van Dijk, J.E., Verheem, A., Akkermans, L.M., Kroese, A.B., & van Erpecum, K.J. (2006). Indomethacin disrupts the protective effect of phosphatidylcholine against bile salt-induced ileal mucosa injury. European Journal of Clinical Investigations 36, 105-112.
- Jørgensen, F., Kroese, A.B. (2005). Ion channel regulation of the dynamical instability of the resting membrane potential in saccular hair cells of the green frog (Rana esculenta). Acta Physiologica Scandinavia 185, 271-290.
- De Jonge, F., De Laet, A., Van Nassauw, L., Brown, J.K., Miller, H.R., van Bogaert, P.P., Timmermans, J.P., & Kroese, A.B. (2004). In vitro activation of murine DRG neurons by CGRP-mediated mucosal mast cell degranulation. American Journal of Physiology; Gastrointest Liver Physiol. 287, G178-191.
- Kuo, J.J., Schonewille, M., Siddique, T., Schults, A.N., Fu, R., Bär, P.R., Anelli, R., Heckman, C.J, & Kroese, A.B. (2004). Hyperexcitability of cultured spinal motoneurons from presymptomatic ALS mice. Journal of Neurophysiology 91, 571-575.
- Prof. Dr. H.G. Gooszen, Dept Surgery, University Medical Centre Utrecht.
- Prof. Dr. J-P. Timmermans, Cell Biology and Histology, University of Antwerp, Belgium.