急性呼吸窘迫综合征（ARDS）死亡率高，其肺组织损伤修复与肺泡巨噬细胞（AM）密切相关：AM在ARDS急性期极化为M1型加重肺损伤，在恢复期转化为M2型促进肺修复。随着肺损伤发展，AM会经历亚型转化表现为M1-M2混合型，但这类AM有何特殊作用还不清楚。我们预实验发现：M1-M2型AM可高表达上皮生长因子HB-EGF；肺损伤后2-5天，肺组织HB-EGF量显著增加。HB-EGF能促进组织修复和Ⅱ型肺泡上皮细胞（AEC2）增殖。因此推测：肺损伤中M1-M2型AM可能通过高表达HB-EGF促进AEC2增殖而启动肺组织修复。本项目拟从细胞及整体动物水平，研究肺损伤中M1-M2型AM是否大量表达HB-EGF，HB-EGF能否促进肺损伤后AEC2增殖、肺泡再生与肺组织修复，其受体EGFR与ERBB4是否介导该作用。本项目将阐释AM由M1向M2转化时促进肺损伤修复的新作用，为ARDS治疗提供新策略。

Acute respiratory distress syndrome (ARDS) is a serious respiratory disorder with significant mortality in patients. The lung injury and repair in ARDS are closely related to alveolar macrophage (AM). It is known that AMs are activated to M1 phenotype at the acute phase of ARDS, resulting in exacerbation of lung injury. While at the resolving phase of ARDS, AMs are polarized to M2 phenotype contributing to repair lung tissue. So in the development of lung injury, AMs can undergo a M1-to-M2 transition in which they exhibit a M1/M2 intermediate polarization (M1-M2) phenotype. However, the special feature and function of M1-M2 AMs are unknown. Our preliminary study showed that M1-M2 AMs expressed a high level of HB-EGF, a kind of epidermal growth factor. In addition, we also found that HB-EGF in lung tissue was significantly increased on the 2th day after the onset of lung injury. It has been reported that HB-EGF can promote tissue repair and stimulate alveolar epithelial cell type Ⅱ (AEC 2) proliferation. Therefore, we establish the hypothesis that M1-M2 AMs can promote AEC 2 proliferation and lung tissue repair through highly expressing HB-EGF in lung injury development. In this study, we would apply the in vivo model of endotoxin-induced acute lung injury in mouse, together with the in vitro model of isolated AMs and AEC 2, to investigate the following questions: (i) whether M1-M2 AMs secrete a high level of HB-EGF in ARDS development; (ii) whether HB-EGF plays a key role in AEC 2 proliferation, alveoli regeneration and lung tissue repair; (iii) whether epidermal growth factor receptor (EGFR) and ERBB4, the receptor of HB-EGF, mediate the repairing effect of HB-EGF in lung injury. In summary, the present study will not only identify a new repairing function of AMs in the transition from M1 to M2, but also provide novel therapeutic strategies for treatment of ARDS.