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Toxicologic Pathology
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Expression of Cytokines and Proteases in Mast Cells in the Lesion of Subcapsular Cell Hyperplasia in Mouse Adrenal Glands

Jong-Soo Kim

National Institute of Industrial Health, Nagao, Tama-ku, Kawasaki, Japan, Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, Japan

Hisayo Kubota

National Institute of Industrial Health, Nagao, Tama-ku, Kawasaki, Japan

Sang-Yoon Nam

Department of Veterinary Anatomy, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, Japan

Kunio Doi

Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, Japan, akunio{at}hongo.ecc.u-tokyo.ac.jp

Junzo Saegusa

National Institute of Industrial Health, Nagao, Tama-ku, Kawasaki, Japan

To examine the possible roles of mast cells in the pathogenesis of subcapsular cell hyperplasia (SCH) in the adrenal glands of mice, we investigated the expression of certain cytokines, including stem cell factor (SCF), tumor necrosis factor-alpha (TNF-{alpha}), nerve growth factor (NGF), and basic fibroblast growth factor (bFGF), and mast cell-specific proteases, such as mouse mast cell protease (mMCP)-2 and mMCP-7. The mRNAs of c-kit (SCF receptor), bFGF, TNF-{alpha}, mMCP-2, and mMCP-7 were expressed in both the adrenal glands and the mouse bone marrow-derived mast cells (mBMMCs). Immunoreactivities for cytokines (SCF, NGF, TNF-{alpha}) and proteases (mMCP-2, mMCP-7) were exclusively located in the mast cells in SCH lesions. The immature mBMMCs did not express the mRNAs of SCF and NGF, whereas the mast cells in the SCH lesions showed the expression of SCF and NGF. These findings suggest that SCH may provide a favorable microenvironment for functional maturation of mast cells to produce SCF and NGF, and the mast cells in SCH lesions synthesize SCF and NGF and may, in part, use them in autocrine fashion for their survival and differentiation. Therefore, mast cells may contribute to SCH pathogenesis by producing a range of multifunctional cytokines and proteases.

Key Words: Mast cell • cytokine • protease • subcapsular cell hyperplasia • adrenal gland • mouse

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Toxicologic Pathology, Vol. 28, No. 2, 297-303 (2000)
DOI: 10.1177/019262330002800209
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