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Footmarks of Innate Immunity in the Ovary and Cytokeratin-Positive Cells as Potential Dendritic Cells

:	Katharina Spanel-Borowski
:	Footmarks of Innate Immunity in the Ovary and Cytokeratin-Positive Cells as Potential Dendritic Cells
:	Springer-Verlag
:	9783642160776
:	Advances in Anatomy, Embryology and Cell Biology
:	1
:	CHF 154.60
:

:	Klinische Fächer
:	English

:	110
:	Wasserzeichen/DRM
:	PC/MAC/eReader/Tablet
:	PDF

The monograph introduces innate immunity as second authority in the ovary besides the endocrine system. Innate immunity appears to orchestrate follicular atresia, follicle rupture, follicle transformation into a corpus luteum (CL) and CL regression through nonsterile inflammation and tissue repair. The concept is new. It centres on cytokeratin-positive (CK+) cells being recognized as a potential nonlymphoid dendritic cell type (DC). Part I describes morphological aspects of immune privilege starting with active hamster ovary implants into the chicken chorioallantois membrane. Follicular atresia and follicle rupture correspond with mild and moderate tissue damage in ovaries of small rodents and rabbits. Superovulations cause severe tissue damage through intraovarian oocyte release with follicle wall remnants in oedema, rupture of vessel walls and thrombosis. The complement system and neuropeptides might play regulatory roles. Part IIa analyzes intact ovaries (cows, human) for the appearance of CK+ cells. In the foetal ovary, sex cords give rise to CK+ cells in primordial follicles. In the adult ovary, CK+ cells are absent in preantral follicles and reappear in mature and regressing follicles. In the CL of early development, steroidogenic CK+ cells build a peripheral zone in the previous granulosa cell layer, and uniformly distribute in the following stages. A microvessel-associated CK+ cell type is seldom found. Part IIb characterizes the morphology and function of CK+ cells in vitro. Isolated from human preovulatory follicles, the epithelioid CK+ granulosa cell subtype regulates TLR4 and CD14 at 36 h of treatment with oxidized lipoprotein (oxLDL, 150 ?mg/ml); nonapoptotic cell death and the increase of reactive oxygen species occur. In contrast, the CK-negative (CK-) granulosa cell type regulates the lectin-like oxLDL receptor 1 (LOX-1) and survival autophagy under oxLDL stimulation. Isolated from bovine CL, the epithelioid CK+ cell type 1 is disclosed as microvascular cell type with a single nonmotile cilium. The microvascular CK+ type strongly upregulates intercellular contacts under treatment with interferon-? (IFN-?). In the CK- cell type 5 of granulosa cell -like appearance, IFN-? treatment supports cell proliferation, N-cadherin upregulation, and the dramatic increase in major histocompatibility complex II peptides (MHC II) by 80-fold compared to basal levels. Type 5 could have been conversed from the steroidogenic CK+ cell type. We summarize and conclude: CK+ granulosa cells express functionally active TLR4, which sense danger signals like oxidative stress in preovulatory follicles and trigger inflammatory and immunoregulatory pathways. The final outcome regulates follicle rupture and transformation into CL. Luteolysis could start by danger-sensing through the microvascular CK+ type 1 cells and the DC-like type 5 cells both sensitive to IFN-?. The future will witness a novel strategy in the therapy of ovarian disorders like anovulations, luteal phase insufficiency, and autoimmune failures

	Preface	6
	Abstract	8
	Acknowledgements	10
	Contents	12
	Abbreviations	14
	Chapter 1: Background	18
	1.1 Innate Immunity, Toll-Like Receptors and Danger Signals	18
	1.2 The Ovary, Tissue Remodeling and Immune Privilege	21
	1.3 Design	23
	Chapter 2: Materials and Methods	24
	2.1 Cyclic and Superovulated Ovaries from Rats, Hamsters, and Rabbits as well as Canine, Bovine and Human Ovaries	24
	2.1.1 Fibrinolytic Activity and Implants on the Chicken Chorioallantoic Membrane	26
	2.1.2 Fixation, Staining and Counting Ovarian Structures	28
	2.2 Cell Culture Subtypes from Follicles Derived from Patients Under IVF Therapy	28
	2.3 Cell Culture Subtypes from Bovine CL and Characterization	31
	Chapter 3: Footmarks of INIM	33
	3.1 The Complement System as Danger Sensor in General and in the Ovary	33
	3.2 Mild Danger with Mild Response	35
	3.2.1 Implantation of the Ovary into the CAM	35
	3.2.2 Follicular Atresia	35
	3.3 Moderate Danger by Preovulatory Follicle Rupture and Acute Inflammation with Eosinophils	37
	3.3.1 Recruitment of Eosinophils and SP-Like Expression	42
	3.4 Severe Danger in Superovulated Ovaries with Intra-ovarian Oocyte Release (IOR) and Thrombus Formation	46
	Chapter 4: Cytokeratin-Positive Cells (CK+) as Potential Dendritic Cells	51
	4.1 Dendritic Cells, the TLR System in General and in the Ovary	51
	4.2 Localization of CK+ Cells in the Intact Ovary	54
	4.2.1 Follicles in Fetal and Adult Ovaries	55
	4.2.2 Corpus Luteum	58
	Chapter 5: Characterization of Isolated CK+ Cells	61
	5.1 CK+ Cells from Preovulatory Follicles with TLR4 Expression	61
	5.2 CK+ Cells from CL in Comparison with CK- Cells	69
	5.2.1 Effects of IFN-gamma on CK+ Cells from the CL Compared to CK- Cells and to Surface Epithelial Cells	78
	5.2.2 Reflections on Quality of the CK+ Type 1 and Similarity with the Type 5	82
	Chapter 6: Working Hypothesis and Challenges	93
	Chapter 7: Clinical Perspectives	99
	Chapter 8: Concluding Summary and Remarks	102
	References	104
	Index	115