The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English German |
| Veröffentlicht: |
2014
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Zsfassung in dt. und engl. Sprache |
| Beschreibung: | 84 S. Ill., graph. Darst. |
Internformat
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV042488180 | ||
| 003 | DE-604 | ||
| 005 | 20180313 | ||
| 007 | t | ||
| 008 | 150408s2014 ad|| m||| 00||| eng d | ||
| 035 | |a (OCoLC)909790030 | ||
| 035 | |a (DE-599)BSZ428402763 | ||
| 040 | |a DE-604 |b ger | ||
| 041 | 0 | |a eng |a ger | |
| 049 | |a DE-188 |a DE-355 |a DE-83 | ||
| 082 | 0 | |a 610 | |
| 100 | 1 | |a Förster, Anja |e Verfasser |0 (DE-588)1064623980 |4 aut | |
| 245 | 1 | 0 | |a The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells |c vorgelegt von Anja Förster |
| 264 | 1 | |c 2014 | |
| 300 | |a 84 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a Zsfassung in dt. und engl. Sprache | ||
| 502 | |a Köln, Univ., Diss., 2014 | ||
| 650 | 0 | 7 | |a Mastzelle |0 (DE-588)4194827-0 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Homöostase |0 (DE-588)4160575-5 |2 gnd |9 rswk-swf |
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 689 | 0 | 0 | |a Homöostase |0 (DE-588)4160575-5 |D s |
| 689 | 0 | 1 | |a Mastzelle |0 (DE-588)4194827-0 |D s |
| 689 | 0 | |5 DE-188 | |
| 856 | 4 | 2 | |m HBZ Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027923016&sequence=000004&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-027923016 | ||
Datensatz im Suchindex
| _version_ | 1804153222037766144 |
|---|---|
| adam_text | Titel: The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells
Autor: Förster, Anja
Jahr: 2014
Table of contents
1 Introduction......................1
1.1 Mast cells.................................................................................................................................1
1.1.1 Development of mast cells..............................................................................................1
1.1.2 Subtypes of mast cells.....................................................................................................1
1.1.3 Activation of mast cells....................................................................................................2
1.1.4 The role of mast cells in immunity and hypersensitivity..................................................3
1.1.5 Mastocytosis....................................................................................................................9
1.1.6 Mouse models of mast cell deficiency and mast cell-specific gene deletion...................6
1.2 Cell death.................................................................................................................................9
1.2.1 Apoptosis.........................................................................................................................9
1.2.2 Necrosis.........................................................................................................................11
1.2.3 Other types of cell death................................................................................................12
1.2.4 Bcl-2 family proteins......................................................................................................12
1.2.5 Mcl-1..............................................................................................................................15
1.2.6 Bcl-xL.............................................................................................................................16
1.2.7 TRAIL-Rs.......................................................................................................................17
1.3 Regulation of cell death in mast cells....................................................................................19
2 Objectives........................................................................................................21
3 Material and Methods......................................................................................22
3.1 Chemicals..............................................................................................................................22
3.2 Buffers...................................................................................................................................22
3.3 Mice.......................................................................................................................................22
3.4 Genotyping............................................................................................................................23
3.4.1 Isolation of genomic tail DNA........................................................................................23
3.4.2 PCR...............................................................................................................................23
3.5 Histology................................................................................................................................24
3.6 Passive systemic anaphylaxis...............................................................................................25
3.7 Cell culture.............................................................................................................................25
3.7.1 WEHI-3B........................................................................................................................25
3.7.2 CHO...........................................................................................................................25
3.7.3 BMMC..................................................................................................................26
3.7.4 PCMC......................................................................................................................................................................................................26
3.7.5 HMC-1 ..........................................................................................................................................................................................26
3.7.6 TF1 ...............................................26
3.8 Flow cytometry.......................................................................................................................27
3.8.1 Analysis of myeloid and lymphoid cells in spleen and peritoneal cavity.......................27
3.8.2 Evaluation of viability and apoptosis by flow cytometry.................................................28
3.8.3 Surface expression of TRAIL-Rs...................................................................................28
3.9 Western blotting.....................................................................................................................29
3.10 Apoptosis of BMMC in response to growth factor deprivation..............................................29
3.11 Viability and apoptosis upon incubation with ActD and etoposide........................................30
3.12 Viability and apoptosis upon incubation with TRAIL..............................................................30
3.13 RT-PCR to detect TRAIL-R transcripts..................................................................................30
3.14 Growth rate of BMMC............................................................................................................31
3.15 ß-Hexosaminidase assay......................................................................................................31
3.16 Statistical analysis.................................................................................................................31
4 Results.............................................................................................................32
4.1 Generation of mast cell-specific Mcl-1, Bcl-x and TRAIL-R knockout mice..........................32
4.2 Mcl-1 serves as central regulator of mast cell homeostasis..................................................34
4.2.1 Mast cell-specific deletion of Mcl-1 results in mast cell deficiency................................34
4.2.2 Numbers of myeloid and lymphoid cells in spleen and peritoneal cavity are not affected
by the Mcpf5Cre-mediated deletion of Mcl-1.................................................................38
4.2.3 Mcpt5Cre/Mcl-1m mice are protected from IgE-mediated passive systemic anaphylaxis
.......................................................................................................................................39
4.3 Bcl-xL participates in the regulation of mast cell survival......................................................41
4.3.1 Mast cell numbers are partially reduced in Mcpt5Cre/Bcl-x mice..............................41
4.3.2 IgE-mediated passive systemic anaphylaxis is not affected in Mcpt5Cre/Bcl-xm mice 43
4.3.3 Bcl-x-deficient mast cells develop in vitro......................................................................43
4.3.4 Mx1Cre/Bcl-x BMMC show absence of Bcl-xL and increased levels of Mcl-1...........45
4.3.5 Deletion of Bcl-x has no impact on apoptosis in response to growth factor deprivations
4.3.6 Apoptosis in response to antineoplastic drugs is increased in Bc/-x-deficient mast cells.
.......................................................................................................................................47
4.3.7 TRAIL-induced apoptosis is increased in Bcl-x-deficient mast cells.............................50
4.4 The function of TRAIL-R is regulated by KIT activation........................................................51
4.4.1 Deletion of TRAIL-R has no impact on turnover of murine mast cells..........................51
4.4.2 IgE-mediated passive systemic anaphylaxis is extended in Mcpt5Cre/TRAIL-Rmmice..
.......................................................................................................................................53
4.4.3 Deletion of TRAIL-R is highly efficient in PCMC and BMMC cultured from TRAIL-Rf°
mice...............................................................................................................................53
4.4.4 Wild type PCMC and BMMC fail to undergo TRAIL-mediated cell death.....................55
4.4.5 Turnover and growth factor deprivation-induced apoptosis are not affected in TRAIL-Rko
BMMC............................................................................................................................55
4.4.6 Deletion of TRAIL-R fails to affect degranulation of mast cells.....................................56
4.4.7 SCF-induced KIT activation enhances the susceptibility towards TRAIL-mediated cell
death..............................................................................................................................57
4.4.8 The extent of activating KIT mutations correlates with the expression of TRAIL-Rs and
the sensitivity towards TRAIL-induced cell death..........................................................58
5 Discussion.......................................................................................................63
5.1 Generation of a new mouse model of mast cell deficiency...................................................63
5.1.1 Other mouse models of mast cell deficiency.................................................................64
5.1.2 Efficiency of mast cell ablation......................................................................................65
5.1.3 Future investigations......................................................................................................66
5.2 Involvement of Bcl-xL in the homeostasis of mast cells........................................................68
5.2.1 Bcl-xL partially ensures the survival of mast cells in vivo..............................................68
5.2.2 Bcl-xL is dispensable for development of mast cells in vitro.........................................69
5.2.3 Absence of Bcl-xL results in upregulation of Mcl-1.......................................................69
5.3 Activation of KIT modulates the function of TRAIL-R in mast cells.......................................72
5.3.1 Discrepancies in TRAIL-R function between human and murine mast cells.................72
5.3.2 Involvement of death receptors in the homeostasis and function of murine mast cells 73
5.3.3 Clinical implication of TRAIL-R regulation.....................................................................73
6 References.......................................................................................................75
|
| any_adam_object | 1 |
| author | Förster, Anja |
| author_GND | (DE-588)1064623980 |
| author_facet | Förster, Anja |
| author_role | aut |
| author_sort | Förster, Anja |
| author_variant | a f af |
| building | Verbundindex |
| bvnumber | BV042488180 |
| ctrlnum | (OCoLC)909790030 (DE-599)BSZ428402763 |
| dewey-full | 610 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 610 - Medicine and health |
| dewey-raw | 610 |
| dewey-search | 610 |
| dewey-sort | 3610 |
| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| format | Thesis Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01404nam a2200361 c 4500</leader><controlfield tag="001">BV042488180</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">20180313 </controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">150408s2014 ad|| m||| 00||| eng d</controlfield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)909790030</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)BSZ428402763</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield><subfield code="a">ger</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-188</subfield><subfield code="a">DE-355</subfield><subfield code="a">DE-83</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">610</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Förster, Anja</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)1064623980</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells</subfield><subfield code="c">vorgelegt von Anja Förster</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2014</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">84 S.</subfield><subfield code="b">Ill., graph. Darst.</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">Zsfassung in dt. und engl. Sprache</subfield></datafield><datafield tag="502" ind1=" " ind2=" "><subfield code="a">Köln, Univ., Diss., 2014</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Mastzelle</subfield><subfield code="0">(DE-588)4194827-0</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Homöostase</subfield><subfield code="0">(DE-588)4160575-5</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="655" ind1=" " ind2="7"><subfield code="0">(DE-588)4113937-9</subfield><subfield code="a">Hochschulschrift</subfield><subfield code="2">gnd-content</subfield></datafield><datafield tag="689" ind1="0" ind2="0"><subfield code="a">Homöostase</subfield><subfield code="0">(DE-588)4160575-5</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="1"><subfield code="a">Mastzelle</subfield><subfield code="0">(DE-588)4194827-0</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2=" "><subfield code="5">DE-188</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">HBZ Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027923016&sequence=000004&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-027923016</subfield></datafield></record></collection> |
| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV042488180 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T01:23:10Z |
| institution | BVB |
| language | English German |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-027923016 |
| oclc_num | 909790030 |
| open_access_boolean | |
| owner | DE-188 DE-355 DE-BY-UBR DE-83 |
| owner_facet | DE-188 DE-355 DE-BY-UBR DE-83 |
| physical | 84 S. Ill., graph. Darst. |
| publishDate | 2014 |
| publishDateSearch | 2014 |
| publishDateSort | 2014 |
| record_format | marc |
| spelling | Förster, Anja Verfasser (DE-588)1064623980 aut The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells vorgelegt von Anja Förster 2014 84 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zsfassung in dt. und engl. Sprache Köln, Univ., Diss., 2014 Mastzelle (DE-588)4194827-0 gnd rswk-swf Homöostase (DE-588)4160575-5 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Homöostase (DE-588)4160575-5 s Mastzelle (DE-588)4194827-0 s DE-188 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027923016&sequence=000004&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Förster, Anja The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells Mastzelle (DE-588)4194827-0 gnd Homöostase (DE-588)4160575-5 gnd |
| subject_GND | (DE-588)4194827-0 (DE-588)4160575-5 (DE-588)4113937-9 |
| title | The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells |
| title_auth | The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells |
| title_exact_search | The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells |
| title_full | The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells vorgelegt von Anja Förster |
| title_fullStr | The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells vorgelegt von Anja Förster |
| title_full_unstemmed | The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells vorgelegt von Anja Förster |
| title_short | The role of pro- and anti-apoptotic proteins for homeostasis and function of mast cells |
| title_sort | the role of pro and anti apoptotic proteins for homeostasis and function of mast cells |
| topic | Mastzelle (DE-588)4194827-0 gnd Homöostase (DE-588)4160575-5 gnd |
| topic_facet | Mastzelle Homöostase Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027923016&sequence=000004&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT forsteranja theroleofproandantiapoptoticproteinsforhomeostasisandfunctionofmastcells |