Mast Cells and Subcapsular Cell Hyperplasia in the Adrenal Glands of Mice : マスト細胞とマウス副腎皮膜下細胞過形成

다국어 초록 (Multilingual Abstract)

Chapter 1
Subcapsular cell hyperplasia (SCH) in the adrenal cortex of aged mice (13-15 months old) was frequent in both sexes of BALB/c, C3H/He, DBA/2J and IQI/Jic mice and in the females of A/J and C57BL/6, although the incidence and severity of SCH were considerably different among mouse strains. Mast cells were closely associated with SCH in the A/J, BALB/c, C57BL/6, DBA/2J and IQI/Jic mice, but not in the C3H/He strain. Compared with other strains, IQI/Jic mice had a significantly larger number of mast cells in the adrenal glands. These findings suggest that mast cells are implicated in the development of SCH in many strains of mouse, and IQI/Jic strain would be appropriate choice for studying the pathogenesis of SCH in the adrenal gland and the role of mast cells in this lesion.
Chapter 2
IQI/Jic mice showed a high incidence of subcapsular cell hyperplasia (SCH) in the adrenal cortex accompanied by prominent mast cell infiltration. SCH-positive animals appeared as early as at 3 months of age, with an incidence of 18% in males and 20% in females. Except for one mouse, all females older than 6 months had the lesion. In males, the incidence increased gradually until 9 months, and was then stable at 75-88% thereafter. The severity of SCH increased with age in both sexes, and the lesions were more prominent in females. Mast cells infiltrated mainly at the sites of SCH, and their density was associated with the severity of the lesion. A quantitative morphometric study confirmed a significant correlation between the severity of SCH and the density of mast cells. A histochemical study demonstrated that these mast cells were of the connective tissue-type. These findings indicate that mast cell may play an important role in the pathogenesis of SCH and, IQI/Jic mouse would be a useful strain to elucidate the pathogenesis of SCH in the adrenal cortex in association with mast cell function.
Chapter 3
To further characterize subcapsualr cell hyperplasia (SCH) in mice, the author evaluated the morphologic characteristics of SCH in female IQI/Jic mice. IQI/Jic mice showed SCH in the adrenal glands as early as 2 months of age. Hyperplastic subcapsular cells synthesized collagen fibrils, and SCH often accompanied by the infiltration of mast cells but not any other inflammatory cells. Generally, hyperplastic subcapsular cells showed different features in intracytoplasmic contents from adrenocortical endocrine cells. However, they also revealed the features similar to adrenocortical endocrine cells that they had some round mitochondria with tubular cristae, desmosome and basement membrane. Occasionally, adrenocortical endocrine cells which showed rather the characteristic features of hyperplastic subcapsualr cells than the normal endocrine cells were observed in advanced SCH lesions. These findings suggest that the hyperplastic cells would be originated from undifferentiated endocrine cells and/or normal endocrine cells of adrenal cortex.
Chapter 4
On the basis of the observations in Chapter 1 and Chapter 2, the author examined the functional significance of mast cell accumulation in the pathogenesis of subcapsular cell hyperplasia (SCH) and the possible interactions between mast cells and hyperplastic cells in the adrenal gland of mice. At first, the author investigated the expression of mRNAs for certain cytokines including SCF and its receptor c-kit, bFGF, NGF, TNF-α; and mast cell-specific proteases such as mMCP-2 and mMCP-7 in the adrenal glands and, for comparison, in the mBMMC. Subsequently, adrenal glands from IQI/Jic mice were evaluated immunohistochemically in GMA tissue sections to identify the expression and localization of their proteins within the SCH lesions.
The mRNA for c-kit (SCF receptor) was detected in the IL-3 dependent immature mast cells (mBMMC) but the mRNA for its ligand SCF was not detected. In contrast, the mRNAs for not only c-kit, bFGF, TNF-α, mMCP-2 and mMCP-7 but also SCF and NGF were detected in the adrenal gland specimens. Immunoreactivities of cytokines (SCF, NGF, TNF-α) and proteases (mMCP-2 and mMCP-7) were observed in the adrenal glands. Moreover, positive staining of them were exclusively located to the mast cells at sites of SCH. These findings indicate that mast cells acquired functional maturity to produce SCF and NGF in the SCH lesions. The results of this study suggest that (1) SCH may provide a favorable microenvironment for mast cell differentiation and maturation, and (2) tissue mast cells in SCH lesions synthesize SCF and NGF, and may use them in autocrine fashion for survival and differentiation, and (3) these mast cells can store a range of multifunctional cytokines and proteases, and they contribute to SCH pathogenesis in the adrenal glands of mice.

목차 (Table of Contents)

• General Introduction = 3
• Chapter 1:Subcapsular cell hyperplasia and mast cell infiltration in the adrenal glands of mice:Comparative study in 7 inbred strains. = 7
• Chapter 2:Correlation of mast cells with subcapsular cell hyperplasia in the adrenal glands of IQI/Jic mice. = 17
• Chapter 3:Histopathological examination of subcapsular cell hyperplasia. = 32
• Chapter 4:Expressions of cytokines and neutral proteases on the mast cells and subcapsular cell hyperplasia in the adrenal glands of mice. = 45
• Concluding Remarks = 63
• Acknowledgements = 67
• References = 68