monograph opus:2699 Tuszynski M.H., U H.S., Amaral D.G., Gage F.H. (1990). " Nerve growth factor infusion in the primate brain reduces lesion-induced cholinergic neuronal degeneration " . J. Neurosci. 10: pp. 3604 – 3614 Wang Y., Hagel C., Hamel W., Miller S., Kluwe L., Westphal M. (1998). " Trk A, B, and C are commonly expressed in human astrocytes and astrocytic gliomas but not by human oligodendrocytes and oligodendroglioma " . Acta Neuropathol. Science 215: pp. 357 – 364 Valenzuela D.M., Maisonpierre P.C., Glass D.J., Rojas E., Nunez L., Kong Y., Gies D.R., Stitt T.N., Ip N.Y., Yancopoulos G.D. (1993). " Alternative forms of rat TrkC with different functional capabilities " . Neuron 10: pp. 963 – 974 Rubio N. (1997). " Mouse astrocytes store and deliver brain-derived neurotrophic factor usin the non-catalytic pg95trkB receptor " . Eur. J. Neurosci. 9: pp. 1847 – 1853 Torcia M., Bracci-Laudiero L., Lucibello M., Nencioni L., Labardi D., Rubartelli A., Cizzolino F., Aloe L., Garaci E. (1996). " Nerve growth factor is an autocrine survival factor for memory B lymphocytes " . Cell 85: pp. 345 - 356 Stadelmann Chr., Kerschensteiner M., Misgeld Th., Brück W., Hohlfeld R., Lassmann H. (2002). " BDNF an gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? " . Brain 125: pp. 75 – 85 Stephens R.M., Loeb D.M., Copeland T.D., Pawson T., Greene L.A., Kaplan D.R. (1994). " Trk receptors use redundant signal transduction pathways involving Shc and PLC-gamma 1 to mediate NGF responses " . Neuron 12: pp. 691 -705 Watson A., Ensor E., Symes A. et al. (1995). " A minimal CGRP gene promotor is inducible by nerve growth factor in adult rat dorsal root ganglion neurons but not in PC12 phaeochromocytoma cells " . Eur. J. Neurosci. 7: pp. 394 – 400 Weskamp G., Otten U. (1987). " An enzyme-linked immunoassay for nerve growth factor (NGF): a tool for studying regulatory mechanisms involved in NGF production in brain and in peripheral tissues " . J. Neurochem. 48: pp. 1779 – 1786 Yuan J., Yanker B.A. (2000). " Apoptosis in the nervous system " . Nature 407: pp. 802 -809 Rolink A., Melchers F. (1996) " B-cell development in the mouse " . Immunology Lett. 54 (2-3): pp. 157 – 161 Rodriguez-Tebar A., Dechant G., Barde Y.A. (1990). " Binding of brain- derived neurotrophic factor to the nerve growth factor receptor " . Neuron 4: pp. 487 – 492 Rolink A., Melchers F. (1993). " B lymphopoiesis in the mouse " . Adv. Immunology 53: pp. 123 – 156 Oppenheim R.W. (1991). " Cell death during development of the nervous system " . Annu. Rev. Neurosci. 14: pp. 453 -501 Riedel K.H., Wingfied B.D., and Britz T.J. (1992). " Combined influence of magnesium concentration and polymerase chain reaction specificity enhancers " . FEMS Microbiol. Lett. 92: 69 – 72 " Continuous fluorescence monitoring of rapid cycle DNA amplification " Bio Techniques 22: 130 – 138 Ultsch M.H., Wiesmann C., Simmons L.C., Henrich J., Yang M., Reilly D., Bass S.H., deVos A.M. (1999). " Crystal structures of the neurotrophin- binding domain of TrkA, TrkB and TrkC " . J. Mol. Biol. 290: pp. 149 – 159 Teichmann JV, Ludwig WD, Thiel E (1992). " Cytotoxicity of interleukin 2- induced lymphokine-activated killer (LAK) cells against human leukemia and augmentation of killing by interferons and tumor necrosis factor " . Leuk Res 16(3):287-98 Yan H., Chao M.V. (1991). " Disruption of cystein-rich repeats of the p75 nerve growth factor receptor leads to loss of ligands binding " . Journal of Biological Chemistry 266: pp. 12099 – 12104 Strada O., Hirsch E.C., Javoy-Agid F., Lehericy S., Ruberg M., Hauw J.J., Agid Y. (1992). " Does loss of nerve growth factor receptors precede loss of cholinergic neurons in Alzheimer´s disease? An autoradiographic study in the human striatum and basal forebrain " . J. Neurosci. 12: pp. 4766 – 4774 Zhang Q., Ji R.R., Lindsay R., Hokfelt T. (1995). " Effect of growth factor on substance P mRNA expression in axotomized dorsal root ganglia " . Neuroreport 6: pp. 1309 – 1312 Tam S.Y., Tsai M., Yamaguchi M., Yano K., Butterfield J.H., Galli S.J. (1997). " Expression of functional TrkA receptor tyrosine kinase in HMC-1 human mast cells line and human mast cells " . 90: pp. 1807 -1820 Taniguchi S., Takigawa M. (1994b). " Expression of trkC in a mouse osteoblastic cell line and response to neurotrophin-3 " . Biochem. Biophys. Pincelli C., Sevignani C., Manfredini R. et al. (1994). " Expression und function of nerve grwoth factor and nerve grwoth factor receptor on cultured keratinocytes " . J. Invest. Dermatology 103: pp. 13 -18 Osawa M., Tokumoto Y., and H. Nakauchi (1996) " Hemapoietic stemm cells " . In Weir´s Handbook of Experimental Immunology, Vol. 2, 5 th Edition. Uharek L, Zeis M, Glass B, Steinmann J, Dreger P, Gassmann W, Schmitz N, Muller-Ruchholtz W. (1996). " High lytic activity against human leukemia cells after activation of allogeneic NK cells by IL-12 and IL-2 " . Leukemia; 10: 1758-1764 Qiagen (1999). " HotStarTaq ™ PCR Handbook; HotStarTaq Master Mix " , Qiagen GmbH 40724 Hilden, pp. 4 – 15 Olgart C., Fossard N. (2001). " Human lung fibroblasts secrete nerve growth factor: effect of inflammatory cytokines and glucocorticoids " . Eur. Respir. J. 18: pp. 115 -121 Xiang Z., Nilsson G. (2000). " IgE receptor-mediated release of nerve growth factor by mast cells " . Clin. Exp. Allergy 30: pp. 1379 -1386 Rabizadeh S., Oh J., Zhong L., Yang J., Bitler C.M., Butcher L.L., Bredesen D.E. (1993). " Induction of apaptosis by the low affinity NGF-receptor " . Science 261: pp. 345 -348 Winkler T.H., Melchers F., Roliink A. (1994). " Interleukin-3 and initerleukin-7 are alternative growth factors for the same B-cell precursors in the mouse " . Blood 85: pp. 2045 – 2051 Zhang Y., Yao B., Delikat S., Bayoumy S., Lin X.H., Basu S., McGinley M., Chan-Hui P.Y., Lichtenstein H., Kolesnick R. (1997). " Kinase suppressor of Ras is ceramide-activated protein kinase " . Cell 89: pp. 63 – 72 Roit M. Ivan, Brostoff J., Male D.K. (1995). " Kurzes Lehrbuch der Immunologie " Georg Thieme Verlag Stuttgart/ New York, 3. neubearbeitete Auflage, Seite 1 – 11 Roche Diagnostic Cooperation (2000). " LightCycler Operator's Manual " Roche Molecular Biochemicals. Version 3.5, pp. 16 – 19; 97 – 121 Osawa M., Hanada K., Hamada H., and Nakauchi H. (1996). " Longterm lymphopoietic reconstitution by a single CD34-low/ negative hemopoietic stem cell " . Science 273: 242 – 245 Sahle A. (2001). " Mambrankontakte von T-Lymphozyten mit dendritischen Zellen in den sekundär lymphatischen Organen der Ratte " . Abt. für Pawelec G. (1994). " MHC-unrestricted immune surveillance of leukemia " . Cancer Biother; 9(3): 265-288 PharMingen (2002). " Mouse CD Chart " . PharMingen, A Becton Dickinson Company 10975 Torreyana Road, San Diego, CA 92121 Wiesmann C., deVos A.M. (2001). " Nerve growth factor: structure und function " . Cell. Mol. Life Sci. 58 (5-6): pp. 748 -759 Nilsson A.S., Fainzilber M., Falck P., Ibanez C.F. (1998). " Neurotrophin-7: a novel member of the neurotrophin family from the zebrafish " . FEBS Lett. 424: pp. 285 -290 Nockher W.A., Renz H. (2006). " Neurotrophins and asthma: novel insight into neuroimmune interaction " . J. Allergy Clin. Immunol. 117 (1): pp. 67 – 71 Otten U., Gadient R.A. (1995). " Neurotrophins and cytokines – intermediaries between the immune and nervous systems " . In. J. Dev. Neurosci. 13: pp.147 Otten U., Scully J.L., Ehrhard P.B., Gadient R.A. (1994). " Neurotrophins: signals between the nervous and immune systems " . Prog. Brain Res. 103: pp. 293 -305 Verdi J.M., Birren S.J., Ibanez C.F., Persson H., Kaplan D.R., Benedetti M., Chao M.V., Snderson D.J. (1994). " p75 LNGRF regulates trk signal transduction and NGF-induced neuronal differentiation in MAH cells " . Neuron 12: pp. 733 – 745 Rodriguez-Viciana P., Warne P.H., Dhand R., Vanhaesebroeck B., Gout I., Fry M.J., Waterfield M.D., Downward J. (1994). " Phosphtidylinositol-3-OH kinase as a direct target of Ras " . Nature 370: pp. 527 -532 Tuszynski M.H., Gage F.H. (1990). " Potential use of neurotrophic agents in the treatment of neurodegenerative disorders " . Acta Neurobiol. Exp. (Wars) 50: pp. 311 – 322 Winkler T.H., Rolink A., Melchers F., Karasyama H. (1995). " Precursor B cells of mouse bone marrow express two different complexes with the surrogat light chain on the surface " . Eur J Immunol 24: pp. 446 -450 Rosenthal A., Goeddel D.V., Nguyen T., Lewis M., Shih A., Laramee G.R., Nikolics K., Winslow J.W. (1990). " Primary structure and biological activity of a novel human neurotrophic factor " . Neuron 4: pp. 767 – 773 Ririe K.M., Rasmussen R.P., and Wittwer C.T. (1997). " Product differentiation by analysis of DNA melting curves during the polymerase chain reaction. " Anal. Biochem. 245: 154 – 160 Qiagen (2002). " QuantiTect ™ SYBR ® Green PCR Handbook; For quantitative, real time PCR and two step RT-PCR " , Qiagen GmbH 40724 Hilden, pp. 6 – 34 Radic M.Z., Zouali M. (1996). " Receptor editing, immune diversification, and self tolerance " . Immunity 5: pp. 505 – 511 Tuszynski M.H., Sang H., Yoshida K., Gage F.H. (1991). " Recombinant human nerve growth factor iinfusions prevent cholinergic neuronal degeneration in the adult primate brain " . Ann. Neurol. 30: pp. 625 – 636 Verheij M., Bose R., Lin X.H., Yao B., Jarvis W.D., Grant S., Birrer M.J., Szabo E., Zon L.I., Kyriakis J.M., Haimovitz-Friedman A., Fuks Z., Kolesnick R.N. (1996). " Requirement for ceramide-initiated SAPK/JNK signalling in stress-iinduced apoptosis " . Nature 380: pp. 75 – 79 Otten U., Goedert M., Mayer N., Lembeck F. (1980). " Requirement of nerve growth factor for development of substance P-containing sensory nerves " . Nature 287: pp. 158 – 159 Yan Q., Snider W.D., Pinzone J.J., Johnson E.M. Jr. (1988). " Retrograde transport of nerve growth factor (NGF) in motoneurons of developing rats: assessment of potential neurotrophic effects " . Neuron 1: pp. 335 – 343 Qiagen (2001). " RNeasy ® Mini handbook " . Qiagen GmbH 40724 Hilden, pp. 10 – 41 Stratagene (2001). " RoboCycler ® Temperatures Cyclers and Accessories, Instruction Manual " . #70183-00, Stratagene, 11011 North Torrey Pines Road La Jolla, CA 92037, United States, pp. 2 -31 Raychaudhuri S.P., Raychaudhuri S.K. (2004). " Role of NGF and neurogenic inflammation in the pathogenesis of psoriasis " . Prog. Brain Res. 146: pp. 433 – 437 Namen A.E., Lupton S., Hjerrild K., Wignall J., Mochizuki D.Y., Schmierer A., Mosley B., March C.J., Urdal D., Gillis S., Cosman D. and Goodwin R.G. (1988). " Stimulation of B-cell progenitors by cloned murine interleukin-7 " . Nature (London) 333: pp. 571 -573 Winkler T.H., Melchers F. (1997). " Structure und function of the pro-and pre- B cell receptors an B-lymphoid lineage precursor cells " . In: Monroe J., Rothenberg E. eds. Molecular biology of B and T cell development. Clifton, NJ: Humana Press Tsuda T., Wong D., Dolovich J., Bienenstock J., Marshall J., Denburg J.A. (1991). " Synergistic effects of nerve growth factor and granulocyte- macrophage colony-stimulating factor on human basophilic cell differentiation " . Blood 77: pp. 971 – 979 Storkus WJ, Dawson JR (1991). " Target structures involved in natural killing (NK): characteristics, distribution, and candidate molecules " . Crit Rev Immunol; 10(5): 393 – 416 Veiby O.P., Jacobsen F.W., Cui L., Lyman S.D., and Jacobsen S.E.W. (1996). " The flt3 ligand promotes the survival of primitive hemopoietic progenitor cells with myeloid as well as B lymphoid potential. " J. Immunol. 157: 2953 -2960 Thorpe L.W., Perez-Polo J.R. (1987). " The influence of nerve growth factor on the in vitro proliferative response of rat spleen lymphocytes " . J. Neurosci. Res. 18: pp. 134 – 139 Ortaldo J.R., Winkler-Pickett R., Mason A.T., and Mason L.H. (1998). " The Ly-49 family: regulation of cytotoxicity snd cytokine production in murine CD3 + cells " . J. Immunol. 160: 1158 – 1165 Noga O., Englmann C., Hanf G., Grutzkau A., Seybold J., Kunkel G. (2003). " The production storage and release of the neurotrophins nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 by human peripheral eosinophils in allergics and non allergics " . Cliin. Exp. Allergy 33: pp. 649 -654 Tsoulfas P., Soppet D., Escandon E., Tessarollo L., Mendoza-Ramirez J.L., Rosenthal A., Nikolics K., Parada L.F. (1993). " The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 in PC-12 cells " . Neuron 10: pp. 975 – 990 Rossner S., Ueberham U., Schliebs R., Perez-Polo J.R., Bigl V. (1998). " The regulation of amyloid precursor protein metabolism by cholinergic mechanisms and neurotrophin receptor signalling " . Prog. Neurobiol. 56: pp. 541 – 569 Renz H. (2001). " The role of neurotrophins in bronchial asthma " . Eur. J. Pharmacol. 429 (1-3): pp. 231 -237 Wiese St., Metzger F., Holtmann B., Sendtner M. (1999). " The role of p75 NTR in modulating neurotrophin survival effects in developing motoneurons " . Eur. J. Neurosci. 11: pp. 1668 – 1676 Thein S.L. and Wallace R.B. (1986). " The use of synthetic oligonucletides as specific hybridization probes in the diagnosis of the genetic disorders " . In: Human genetic disease: A practical Approach (ed. K.E. Davies), pp. 33 – 50. Watson F.L., Porcionatto M.A., Bhattacharyya A., Stiles C.D., Segal R.A. (1999). " TrkA glycosylation regulates receptor localization and activity " . J. Neurobil. 39: pp. 323 – 336 Patapoutian A., Reichardt L.F. (2001). " Trk receptors: mediators of neurotrophin action " . Curr. Opin. Neurobiol. 11: pp. 272 -280 " Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells. " Nature 426: pp. 74 – 78 Rolink A., Karasyama H., Haasner D., et al. (1994). " Two pathways B lymphocyte development in mouse bone marrow and the role of surrogate L chain in this development " . Immunol. Rev. 137: pp. 185 – 201 Suggs S.V., Hirose T., Miyake T., Kawashima E.H., Johnson M.J., Itakura K., and Wallace R.B. (1981). " Use of synthetic oligodesoxyribonucleotides for the isolation of specific cloned DNA sequences " . In: Developmental biology using purified genes (ed. D.D. Brown), pp. 683 – 693. Academic Press, New York Pearce F.L., Thompson H.L. (1986). " Some characteristics of histamine secretion from rat peritoneal mast cells stimulated with nerve growth factor " . J. Physiol. 372: pp. 397 -412 Otten U., Erhard P., Peck R. (1989). " Nerve growth factor induces growth and differentiation of human B lymphocytes " . Proc. Natl. Acad. Sci. 86: pp. 10056 – 10063 Obermeier A., Bradshaw R.A., Seedorf K., Choidas A., Schlessinger J., Ullrich A. (1994). " Neuronal differentiation signals are controlles by nerve growth factor receptor/ Trk binding sites for Shc and PLC gamma " . EMBO J. 13: 1585 – 1590 German Brain-derived neurotrophic factor Analysis of neurotrophin and neurotrophin- receptor expression of murine b-cells in bone marrow and spleen of C57BL/6 wildtype mice NT-3 Real time quantitative PCR Untersuchungen der Expression von Neurotrophinen und Neurotrophin-Rezeptoren auf murinen B-Zellen im Knochenmark und in der Milz von C57BL/6 Medical sciences Medicine Medizin trkA NT-3 Nervenwachstumsfaktor Medizin trkC 2010-04-27 https://archiv.ub.uni-marburg.de/diss/z2010/0239/cover.png Neurotrophin-Rezeptor 2010 https://doi.org/10.17192/z2010.0239 trkC Physiologische Chemie ppn:222877286 Neurotrophine sind lösliche, nicht kovalent gebundene Homodimerpeptide, die initial im Zentralnervensystem von Vertebraten detektiert worden sind. Sie vermitteln dort in erster Linie anti-apoptotische Effekte wie Proliferation, Differenzierung, Überleben der Zelle und Schutz vor zytotoxischen Zellschaden; daneben sind auch nicht-topische Effekte wie Induktion von Chemotaxis zur regelrechten Axonsprossung bekannt. Hauptvertreter sind NGF, BDNF, NT-3 und NT-4/5. Dabei werden Neurotrophine nicht nur die Zielzelle umgebenen Zellen sezerniert, sondern auch durch die Zielzelle selbst im Sinne autokriner Mechanismen. Die Effekte der Neurotrophine werden durch zwei Familien von Neurotrophine-Rezeptoren vermittelt: die Tyrosinkinase-Glykoprotein-Rezeptoren binden nur bestimmte Neurotrophine mit hoher Affinität und vermitteln anti-apoptotische Effekte. Sie werden in 3 Klassen unterschieden: trkA, trkB und trkC. Dabei werden durch die Zielzelle durch alternatives Splicing verschiedene Isoformen dieser Rezeptoren exprimiert, darunter auch solche die keine katalytische Tyrosinkinase-Domäne beinhalten. Ein weiterer Rezeptor ist der Pan-Neurotrophin-p75-Rezeptor, der alle Neurotrophine mit gleicher Affinität bindet. Er vermittelt bivalente Funktionen: bei Anwesenheit von trk-Rezeptoren antia-apoptotische Effekte, bei Abwesenheit von trk-Rezeptoren pro-apoptototische Effekte. In den letzten 20 Jahren wurde etraneuronal insbesondere auf Immunzellen Neurotrophin-Synthese und Neurotrophin-Rezeptor-Expression detektiert. Hinsichtlich der B-Zellen zeigen sich jedoch divergente Angaben. Einige Autoren belegen, daß die B-Zelle alle Neurotrophine und deren Rezeptoren exprimiert, andere Autoren belegen lediglich eine Expression von trkA und p75. Dabei sind in diesen Arbeiten einige Limitationen offensichtlich: Verwendung von malignen B-Zellen bzw- EBV-transformierten B-Zellen und Verwendung immunhistochemischer Nachweisverfahren. In dieser Arbeit wurde mittels molekularbiologischer Methodik eine umfassende Charakterisierung der unreifen B-Zellen des Knochenmarks und reifer B-Zellen (exemplarisch in der Milz) in einer Wildtyp-Maus verwirklicht. Dabei zeigt sich, daß reife wie unreife B-Zellen alle bekannten Neurotrophine und deren Rezeptoren exprimiert. Eine Ausnahme besteht jedoch hinsichtlich des trkB-Rezeptors; dieser wird nur in einer Isoform exprimiert, die keine katalytische Tyrosinkinase-Domäne besitzt (trkBgp95). In der quantitativen real-time-PCR zeigt sich, daß BDNF das dominante Neurotrophin der unreifen B-Zelle im Knochenmark und NT-3 und NGF das dominante Neurotrophin der reifen B-Zelle ist. Hinsichtlich der Neurotrophin-Rezeptoren gibt es keine quantitativen Unterschiede, lediglich der Neurotrophin-Rezeptor trkC wird geringradig mehr durch die unreifen B-Zellen des Knochenmarks exprimiert. Milz trkA FACS trkBgp95 NT-4/5 FACS ths Prof. Dr. med. Renz Harald Renz, Harald (Prof. Dr. med.) 2019-08-29 trkBgp145 Knochenmark NT-4/5 Neurotrophine Polymerase-Kettenreaktion Publikationsserver der Universitätsbibliothek Marburg Universitätsbibliothek Marburg doctoralThesis neurotrophin-receptor 186 application/pdf neurotrophine B-Zelle Neurotrophins are essential for survival, proliferation and differentiation for neuronal cells. The neurotrophins are NGF, BDNF, NT-3 and NT-4/5. The effects are mediated by two families of neurotrophin-receptors: the Tyrosinkinase-receptors (trk-receptors) mediated survival, proliferation and differentiation. They only bind with highly affinity certain neurotrophins (for example: NGF is the natural ligand of trkA). It exists three classes of trk-receptors: trkA, trkB and trkC. The trk-receptors are exprimited in different isoforms, some of these isoforms contain no catalytic tyrosinkinase-domain. Another neurotrophin-receptor is the pan-neurotrophin-recetor p75. The p75-receptor mediates different functions: in presence of trk-receptors the p75-recetor causes survival, proliferation and differentiation; in absence of the trk-receptos p75 induces apoptosis. In the last twenty years neurotrophins and their receptors could detected in extraneuronal cells, forthermore in T- and B-lymphocytes. Regard to the b-cells they exist different messages: some authors show us, that b-cells exprimites all neurotrophins and all neurotrophin-receptos, other authors prove only an trkA- and p75 expression of b-cells. We could show with molecular methods (including real-time PCR), that immature and mature b-cells exprimites all neurotrophins and all neurotrophin-receptors. Only the trkB-receptor is exprimited as an isoform: the trkBgp95. This isofoms doesn´t contain a catalytic domain. The dominant neurotrophin of immature b-cells in bone marrow is BDNF. NT-3 and NGF are the dominant neurotrophins of mature b-cells in spleen. urn:nbn:de:hebis:04-z2010-02392 trkBgp145 Emmel, Jörg Emmel Jörg trkBgp95 2010-02-25 Philipps-Universität Marburg