Involvement of the IP-10 chemokine in sarcoid granulomatous reactions.
Involvement of the IP-10 chemokine in sarcoid granulomatous reactions.
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DOI：
10.4049/jimmunol.161.11.6413
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发表时间：
1998-12
影响因子：
4.4
通讯作者：
Carlo Agostini;M. Cassatella;R. Zambello;L. Trentin;S. Gasperini;Alessandra Perin;F. Piazza;M. Siviero;M. Facco;Michelle Dziejman;M. Chilosi;Shixin Qin;A. Luster;G. Semenzato
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文献类型：
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作者：
Carlo Agostini;M. Cassatella;R. Zambello;L. Trentin;S. Gasperini;Alessandra Perin;F. Piazza;M. Siviero;M. Facco;Michelle Dziejman;M. Chilosi;Shixin Qin;A. Luster;G. Semenzato
T细胞和单核细胞在进行性炎症部位的积聚代表了导致结节病肉芽肿形成的一系列事件中的最早步骤。在这项研究中，我们评估了IFN-诱导蛋白10（IP-10）的肺生产，CXC趋化因子，刺激活化T细胞的定向迁移。与非活动性疾病患者或对照组相比，24例肺结节病和淋巴细胞性肺泡炎患者的支气管肺泡灌洗液（BAL）中IP-10水平显著升高。IP-10水平与BAL中类肉瘤CD 45 R 0 +/CD 4+细胞数量呈正相关。在淋巴结中用抗人IP-10多克隆抗体进行的免疫化学显示突出的肉样瘤肉芽肿，显示携带IP-10的细胞主要是位于肉芽肿区域内的上皮样细胞和CD 68+巨噬细胞。从结节病患者的BAL中回收的巨噬细胞对IP-10蛋白染色呈阳性。此外，从患有T细胞肺泡炎的结节病患者分离的肺泡巨噬细胞在IFN-γ存在下培养24小时，分泌能够诱导T细胞趋化性的确定水平的IP-10。有趣的是，从活动性结节病患者中回收的肺泡淋巴细胞是表达Th 1细胞因子（IL-2和IFN-γ）和高水平CXCR 3的CD 4 + T细胞。总之，这些数据表明IP-10在调节T细胞向结节病炎症过程和随后的肉芽肿形成的位点的迁移和活化中的潜在作用。
The accumulation of T cells and monocytes at sites of ongoing inflammation represents the earliest step in the series of events that lead to granuloma formation in sarcoidosis. In this study, we evaluated the pulmonary production of IFN-inducible protein 10 (IP-10), a CXC chemokine that stimulates the directional migration of activated T cells. Striking levels of IP-10 were demonstrated in the bronchoalveolar lavage (BAL) fluid of 24 patients with pulmonary sarcoidosis and lymphocytic alveolitis, as compared with patients with inactive disease or control subjects. A positive correlation was demonstrated between IP-10 levels and the number of sarcoid CD45R0+/CD4+ cells in the BAL. Immunochemistry, performed with an anti-human IP-10 polyclonal Ab in lymph nodes displaying prominent sarcoid granulomas, showed that cells bearing IP-10 were mainly epithelioid cells and CD68+ macrophages located inside granulomatous areas. Macrophages recovered from the BAL of sarcoid patients stained positive for IP-10 protein. Furthermore, alveolar macrophages isolated from sarcoid patients with T cell alveolitis and cultured for 24 h in presence of IFN-gamma secreted definite levels of IP-10 capable of inducing T cell chemiotaxis. Interestingly, alveolar lymphocytes recovered from patients with active sarcoidosis were CD4+ T cells expressing Th1 cytokines (IL-2 and IFN-gamma) and high levels of CXCR3. Taken together, these data suggest the potential role of IP-10 in regulating the migration and activation of T cells toward sites of sarcoid inflammatory process and the consequent granuloma formation.