Nakamura H, Koji T, Tominaga M, Kawakami A, Migita K, Kawabe Y, Nakamura T, Shirabe S, Eguchi K
First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki City, Japan.
Clin Exp Immunol. 1998 Oct;114(1):106-12. doi: 10.1046/j.1365-2249.1998.00692.x.
Apoptosis is a type of cell death that occurs during morphogenesis and development of the immune system. One of the mechanisms is mediated through the Fas and Fas ligand (FasL) pathway. To determine the possible involvement of Fas and its ligand in salivary gland destruction, we analysed the appearance of nuclei with DNA fragmentation by using nick end labelling (TUNEL) and the expression of Fas and FasL by immunohistochemistry in labial salivary glands. Furthermore, we compared the features of apoptosis in labial salivary glands between HTLV-I- and HTLV-I+ SS. When the frozen sections of 10 primary SS patients in the absence of anti-HTLV-I antibody were examined, several apoptotic cells were found in the acinar and ductal epithelial cells as well as infiltrated mononuclear cells. Both Fas and FasL were detected in the infiltrated mononuclear cells. Acinar epithelial cells, which are surrounded by FasL+ mononuclear cells, were also double-positive with Fas and FasL, although the expression of FasL was localized at their apical border, suggesting that apoptosis of mononuclear cells was achieved by activation-induced mechanisms through Fas/FasL pathways, and that of acinar epithelial cells was mediated by FasL derived from either acinar epithelial cells themselves or infiltrated mononuclear cells. Interestingly, Fas expression in ductal epithelial cells was localized around the lumen side of the ducts, indicating that FasL secreted from acinar epithelial cells may induce Fas-mediated apoptosis of ductal epithelial cells. We also studied the labial salivary glands from nine SS patients with anti-HTLV-I antibodies. There was no significant difference in the occurrence of apoptotic cells or in the expression of Fas and FasL between HTLV-I+ and HTLV-I- SS patients. It was of note that neither the expression of Fas and FasL nor the presence of apoptotic cells were determined in labial salivary glands from subjects without SS. These findings indicate that Fas-mediated apoptosis in salivary glands could be involved in the pathological manifestations of SS, irrespective of HTLV-I seropositivity.
细胞凋亡是一种在免疫系统的形态发生和发育过程中发生的细胞死亡类型。其中一种机制是通过Fas和Fas配体（FasL）途径介导的。为了确定Fas及其配体在唾液腺破坏中可能的作用，我们通过缺口末端标记法（TUNEL）分析了DNA片段化的细胞核的出现情况，并通过免疫组织化学法检测了唇唾液腺中Fas和FasL的表达。此外，我们比较了HTLV-I阴性和HTLV-I阳性干燥综合征患者唇唾液腺中细胞凋亡的特征。当检查10例未检测到抗HTLV-I抗体的原发性干燥综合征患者的冰冻切片时，在腺泡和导管上皮细胞以及浸润的单核细胞中发现了几个凋亡细胞。浸润的单核细胞中同时检测到Fas和FasL。被FasL阳性单核细胞包围的腺泡上皮细胞Fas和FasL也呈双阳性，尽管FasL的表达定位于其顶端边界，这表明单核细胞的凋亡是通过Fas/FasL途径的激活诱导机制实现的，而腺泡上皮细胞的凋亡是由腺泡上皮细胞自身或浸润的单核细胞衍生的FasL介导的。有趣的是，导管上皮细胞中的Fas表达定位于导管腔侧周围，这表明腺泡上皮细胞分泌的FasL可能诱导Fas介导的导管上皮细胞凋亡。我们还研究了9例抗HTLV-I抗体阳性的干燥综合征患者的唇唾液腺。HTLV-I阳性和HTLV-I阴性干燥综合征患者之间凋亡细胞的发生率或Fas和FasL的表达没有显著差异。值得注意的是，在无干燥综合征受试者的唇唾液腺中未检测到Fas和FasL的表达，也未发现凋亡细胞。这些发现表明，无论HTLV-I血清学阳性与否，唾液腺中Fas介导的细胞凋亡可能参与了干燥综合征的病理表现。
