Hayashi Y, Yayagi K, Haneji N
Department of Pathology, Tokushima University School of Dentistry, Japan.
Arch Immunol Ther Exp (Warsz). 2000;48(5):399-403.
Sjögren syndrome (SS) is an autoimmune disease characterized by diffuse lymphoid cell infiltrates in the salivary and lacrimal glands, resulting in symptoms of dry mouth and eyes due to insufficient secretion. Although it has been assumed that a combination of immunologic, genetic and environmental factors may play a key role in the development of autoimmune lesions in the salivary and lacrimal glands, little is known about the disease pathogenesis of SS in humans. We have identified the 120 kDa alpha-fodrin as an important autoantigen in the development of SS in both an animal model and SS patients, but the mechanism of alpha-fodrin cleavage leading to tissue destruction in SS remains unclear. Tissue-infiltrating CD4+ T cells purified from the salivary glands of a mouse model for SS bear a large proportion of Fas ligand and the salivary gland duct cells possess apoptotic receptor Fas. Anti-Fas antibody-induced apoptotic salivary gland cells result in specific alpha-fodrin cleavage to the 120 kDa fragment in vitro. Preincubation with a combination of calpain and caspase inhibitor peptides could be responsible for inhibition of the 120 kDa alpha-fodrin cleavage. Thus, an increase in apoptotic protease activities including calpain and caspases may be involved in the progression of alpha-fodrin proteolysis and tissue destruction in the development of SS.
干燥综合征（SS）是一种自身免疫性疾病，其特征是唾液腺和泪腺中出现弥漫性淋巴细胞浸润，由于分泌不足导致口干和眼干症状。尽管人们认为免疫、遗传和环境因素的综合作用可能在唾液腺和泪腺自身免疫性病变的发展中起关键作用，但关于人类SS的发病机制知之甚少。我们已经确定120 kDa的α-血影蛋白是动物模型和SS患者中SS发展的重要自身抗原，但α-血影蛋白裂解导致SS组织破坏的机制仍不清楚。从SS小鼠模型的唾液腺中纯化的组织浸润性CD4 + T细胞含有很大比例的Fas配体，并且唾液腺导管细胞具有凋亡受体Fas。抗Fas抗体诱导的凋亡唾液腺细胞在体外导致特定的α-血影蛋白裂解为120 kDa片段。用钙蛋白酶和半胱天冬酶抑制剂肽的组合进行预孵育可能负责抑制120 kDaα-血影蛋白的裂解。因此，包括钙蛋白酶和半胱天冬酶在内的凋亡蛋白酶活性的增加可能参与了SS发展过程中α-血影蛋白的蛋白水解和组织破坏的进程。
