Expression of IFNγ, coexpression of TNFα and matrix metalloproteinases and apoptosis of T lymphocytes and macrophages in granuloma annulare
Expression of IFNγ, coexpression of TNFα and matrix metalloproteinases and apoptosis of T lymphocytes and macrophages in granuloma annulare
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DOI：
10.1007/s004030000150
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发表时间：
2000-08-01
影响因子：
3
通讯作者：
Berger, H
中科院分区：
文献类型：
--
作者：
Fayyazi, A;Schweyer, S;Berger, H
环状肉芽肿是一种典型的非感染性肉芽肿性皮炎，其形态学特征是坏死核心周围有细胞浸润。由于与结核病的许多形态学相似性，环状肉芽肿被认为代表了一种迟发型超敏反应（Th 1），在此过程中，炎性细胞引起基质降解，在本研究中，我们（1）研究了作为最重要的Th 1相关细胞因子的干扰素-γ的表达，（2）寻找促炎细胞因子肿瘤坏死因子-a和精氨酸调节的基质金属蛋白酶2共表达的原位证据（明胶酶A）和9（明胶酶B），和（3）试图确定在环状肉芽肿的坏死区域内看到的萎缩细胞是否是凋亡细胞。原位杂交结合免疫荧光显示大量浸润的CD 3（+）淋巴细胞表达干扰素-γ，催化信号放大技术在免疫检测中的应用表明，绝大多数CD 3（+）淋巴细胞和CD 68（+）巨噬细胞含有肿瘤坏死因子-α。免疫组化显示产生肿瘤坏死因子-α的巨噬细胞共表达基质金属蛋白酶2和9。原位末端标记结合免疫荧光检测到血管周围区域的少数凋亡T细胞和坏死区的大量凋亡巨噬细胞，这些结果表明，在环状肉芽肿中，干扰素-γ（+）Th-1淋巴细胞可能引起迟发性-型超敏反应，由此巨噬细胞分化为表达肿瘤坏死因子-α和基质金属蛋白酶的侵袭性效应细胞。同时，淋巴细胞和巨噬细胞中的活化诱导的凋亡可用于限制炎性细胞的破坏潜力。
Granuloma annulare, a prototype noninfectious granulomatous dermatitis, is morphologically characterized by a necrobiotic core surrounded by a cellular infiltrate, Because of many morphological similarities to tuberculosis, granuloma annulare has been suggested to represent a delayed-type hypersensitivity (Th1) reaction in the course of which inflammatory cells elicit matrix degradation, In the present study we (1) investigated the expression of interferon-gamma as the most important Th1-associated cytokine, (2) sought in situ evidence for the coexpression of the proinflammatory cytokine tumor necrosis factor-a and cytokine-regulated matrix metalloproteinases 2 (gelatinase A) and 9 (gelatinase B), and (3) sought to determine whether shrunken cells seen within necrobiotic areas of granuloma annulare are apoptotic cells, In situ hybridization combined with immunofluorescence showed that large numbers of infiltrating CD3(+) lymphocytes express interferon-gamma, Application of catalyzed signal amplification in immunodetection revealed that the vast majority of CD3(+) lymphocytes and CD68(+) macrophages contained tumor necrosis factor-alpha. Immunohistochemistry demonstrated that macrophages producing tumor necrosis factor-ct coexpress matrix metalloproteinases 2 and 9, In situ end-labeling combined with immunofluorescence detected few apoptotic T cells in perivascular regions and numerous apoptotic macrophages within necrobiotic areas, These results suggest that in granuloma annulare interferon-gamma(+) Th-1 lymphocytes may cause a delayed-type hypersensitivity reaction whereby macrophages are differentiated to aggressive effector cells expressing tumor necrosis factor-alpha and matrix metalloproteinases, In parallel, activation-induced apoptosis in lymphocytes and macrophages may serve to restrict the destructive potential of the inflammatory cells.