Therapeutic application of lung collectin in acute lung injury

本课题旨在阐明toll样受体（Toll-like receptor, TLRs）对药物性急性肺损伤（drug-induced acute lung injury， ALI）的调控机制，评价肺a集合SP-A的保护作用，为其临床应用奠定分子基础。博莱霉素（BLM）给药SP-A（-/-）小鼠的死亡率明显高于野生型，肺部炎症细胞因子的增加明显高于野生型。SP-A抑制blm诱导的大鼠肺泡巨噬细胞炎症因子。sTLR2基因转染的HEK293细胞NF-kB表达上调。BML直接与sTLR2结合，其结合被SP-A阻断。这些结果表明，blm诱导的信号依赖于TLR2和肺收集，SP-A通过TLR2依赖的信号通路对ALI具有保护作用。

The purpose of this project were to clarify the mechanism of regulation by which Toll-like receptors (TLRs) act against drug-induced acute lung injury (ALI), to evaluate the protective effect by lung a collectin, SP-A and to establish the molecular basis for the clinical application of it. Bleomycin (BLM)-administered SP-A(-/-) mice had significantly higher mortality rate and more increase of inflammatory cytokines in the lungs than wild types. SP-A inhibited BLM-induced inflammatory cytokines from rat alveolar macrophages. sTLR2 gene-transfected HEK293 cells showed up-regulation of NF-kB. BML bound directly with sTLR2 and its binding was blocked by SP-A. These results indicate that BLM-induced signal depends on TLR2 and lung collectin, SP-A has protective function against ALI via TLR2 dependent signal pathway.