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原发性干燥综合征患者唾液腺中Fas及Fas配体的表达

Fas and Fas ligand expression in the salivary glands of patients with primary Sjögren's syndrome.

作者信息

Kong L, Ogawa N, Nakabayashi T, Liu G T, D'Souza E, McGuff H S, Guerrero D, Talal N, Dang H

机构信息

University of Texas Health Science Center, San Antonio 78284-7874, USA.

出版信息

Arthritis Rheum. 1997 Jan;40(1):87-97. doi: 10.1002/art.1780400113.

DOI:10.1002/art.1780400113
PMID:9008604
Abstract

OBJECTIVE

To assess the role of Fas-mediated apoptosis in the salivary glands of patients with primary Sjögren's syndrome (SS).

METHODS

Expression of Fas, Fas ligand (FasL), and bcl-2 in salivary gland biopsy material was detected in situ by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. DNA fragmentation in apoptotic cells was assessed by the enzymatic incorporation of labeled nucleotides (digoxigenin-dUTP).

RESULTS

The acinar epithelial cells in SS were Fas+ and FasL+, and these cells died by apoptosis. The majority of infiltrating lymphocytes in SS were Fas+ and bcl-2+, while few lymphocytes expressed FasL. In situ detection of apoptosis showed minimal cell death of lymphocytes, particularly in dense periductal foci. Lymphocytic cell death was significantly lower (P < 0.0001) in these foci compared with that in the interstitium.

CONCLUSION

Infiltrating lymphocytes in the focal lesions of the salivary glands of patients with SS are blocked in their ability to commit to apoptosis, even though they may express Fas. The presence of bcl-2 in these cells may explain their inability to undergo apoptosis. The acinar epithelial cells, in contrast, may undergo Fas-mediated apoptosis. These results suggest that the Fas death pathway may be an important mechanism leading to the glandular destruction found in SS.

摘要

目的

评估Fas介导的细胞凋亡在原发性干燥综合征(SS)患者唾液腺中的作用。

方法

通过免疫组织化学染色和逆转录-聚合酶链反应原位检测唾液腺活检材料中Fas、Fas配体(FasL)和bcl-2的表达。通过标记核苷酸(地高辛-dUTP)的酶促掺入评估凋亡细胞中的DNA片段化。

结果

SS患者的腺泡上皮细胞Fas+且FasL+,这些细胞通过凋亡死亡。SS中大多数浸润淋巴细胞Fas+且bcl-2+,而很少有淋巴细胞表达FasL。凋亡的原位检测显示淋巴细胞的细胞死亡极少,尤其是在密集的导管周围病灶中。与间质相比,这些病灶中的淋巴细胞死亡明显更低(P < 0.0001)。

结论

SS患者唾液腺局灶性病变中的浸润淋巴细胞尽管可能表达Fas,但其凋亡能力受阻。这些细胞中bcl-2的存在可能解释了它们无法发生凋亡的原因。相比之下,腺泡上皮细胞可能经历Fas介导的凋亡。这些结果表明,Fas死亡途径可能是导致SS中腺泡破坏的重要机制。

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