Blockade of secondary lymphoid tissue chemokine exacerbates Propionibacterium acnes-induced acute lung inflammation
Blockade of secondary lymphoid tissue chemokine exacerbates Propionibacterium acnes-induced acute lung inflammation
复制标题
DOI：
10.4049/jimmunol.166.3.2071
复制
发表时间：
2001-02-01
影响因子：
4.4
通讯作者：
Matsushima, K
中科院分区：
文献类型：
--
作者：
Itakura, M;Tokuda, A;Matsushima, K
趋化因子-趋化因子受体相互作用在白细胞/树突状细胞（DC）运输炎症和免疫应答中起重要作用。我们研究了次级淋巴组织趋化因子（SLC; CCL 21）和巨噬细胞炎性蛋白-2（MIP-2）在由痤疮丙酸杆菌诱导的小鼠急性肺部炎症发展中的病理生理作用。免疫组化结果显示，SLC在正常小鼠支气管周围和血管周围炎性细胞中呈组成性表达，MIP-2阳性细胞在P1 acnes感染小鼠肺泡腔中可见。在P1 acnes Ag感染前注射MIP-2和CXC趋化因子受体2的中和抗体，可减轻P1 acnes诱导的肺部炎症反应。另一方面，多克隆抗SLC Abs（pAbs）加重了肺部炎症。在痤疮丙酸杆菌Ag攻击的肺中，成熟DC（MHC II类+、CD 11 c（+）和CD 86（+））以及巨噬细胞和中性粒细胞的数量增加，而CD 4（+）T细胞（包括记忆T细胞）的数量减少。成熟和增殖的CD 4（+）T细胞数量与用对照Abs处理的小鼠相比，用抗SLC pAbs注射的小鼠中局部淋巴结中的（溴脱氧尿苷（+）CD 4（+））减少。体外增殖测定证实了用抗SLC pAbs处理的小鼠的局部淋巴结中Ag特异性T细胞应答的损害，这些结果首次表明SLC募集的成熟DC在桥接肺中的急性炎症反应（先天免疫）和获得性免疫中的调节作用。
Chemokine-chemokine receptor interaction plays an essential role in leukocyte/dendritic cell(DC) trafficking in inflammation and immune responses. We investigated the pathophysiological roles of secondary lymphoid tissue chemokine (SLC; CCL21) and macrophage inflammatory protein-2 (MIP-2) in the development of acute pulmonary inflammation induced by an intratracheal injection of Propionibacterium acnes in mice. Immunohistochemical studies revealed that SLC was constitutively expressed in the peribronchial areas and perivascular lymphatics in normal mice, MIP-2-positive cells were observed in alveolar spaces in mice challenged with P, acnes, Both neutralization Abs against MIP-2 and CXC chemokine receptor 2 alleviated the P, acnes-induced pulmonary inflammation when injected before P, acnes Ag challenge. On the other hand, polyclonal anti-SLC Abs (pAbs) exacerbated the pulmonary inflammation. The numbers of mature DCs (MHC class II+, CD11c(+), and CD86(+)) as well as macrophages and neutrophils in the P, acnes Ag-challenged lungs were increased, whereas the number of CD4(+) T cells, including memory T cells, was decreased. The numbers of mature and proliferating CD4(+) T cells (bromodeoxyuridine(+)CD4(+)) in regional lymph nodes were decreased in mice injected with anti-SLC pAbs compared with those in mire treated with control Abs, An in vitro proliferation assay confirmed the impairment of the Ag-specific T cell response in regional lymph nodes of mice treated with anti-SLC pAbs, These results indicate for the first time a regulatory role for SLC-recruited mature DCs in bridging an acute inflammatory response (innate immunity) and acquired immunity in the lung.