The Expression And Role Of Scavenger Receptor Class A In Mice With Acute Lung Injury Induced By LPS

We observed the expression of scavenger receptor class A (SR-A) in lung tissue and alveolar macrophage(AM) in mice with acute lung injury induced by Lipopolysaccharide (LPS). The mice received an intraperitoneal(ip) injection of LPS (5 mg/kg). We investigated it's role of clearing LPS and effect on macrophage to produce inflammation cytokines. In addition, by the study on mouse macrophage line J774A.1, after enhancing the expression of SR-A on macrophage, we investigated if it contribute to clearing LPS and decreasing the production of inflammation cytokines, and to determine the roles and mechanisms of SR-A .Main results showed: ①SR-A was widely expression in mouse lung, including alveolar macrophage, pulmonary vascular endothelial cells, vascular smooth muscle cells, lung epithelial, polymorphonuclear neutrophil. Immunohistochemical staining showed that, during the course of ALI developing, the SR-A expression was gradually down-regulated with the time after ip injection LPS, the separated AM show the same result. while groups 4h and 8h, showed remarked one. In vitro, after treated with LPS, expression of SR-A on J774A.1 cells decreased just as on AM. ②LPS coule be detected in the lung at 30min after ip injection LPS, the level was 11.09±2.76EU/ml, there were no difference among the groups of mice at 1h,2h,4h,8h after ip injection LPS. ③The levels of TNF-αin the lung was up-regulated gradually in time dependent fashion. Compared with the level in the lung of saline-instilled animals, the level of TNF-αin the lung of LPS-injected mice increased significantly , the peak expression appeared at 2h after ip injection of LPS. ④PMA can up-regulated macrophage SR-A expression. ⑤After increasing the expression of SR-A by PMA , we added LPS to serum-free medium,and detected the levels of LPS in the medium. The result showed that the levels of LPS was lower in PMA groups than in PMA-free groups. In addition, we found the effect can be restrained by SR-A mAb(2F8). ⑥ELISA results showed that, in the serum-free medium without LPS, the level of TNF-αwas very low; increased when LPS was added. The level of TNF-αincreased significantly, and up-regulated gradually in a time dependent fashion. The peak expression appeared at 1hafter treatment with LPS. Pretreatment with PMA, challenged with LPS,the levels of TNF-αdeduced significantly compared with the groups TPA-free in medium. We also found the effect can be hold back by SR-A mAb(2F8).The results suggest: ①During the course of ALI, the expression of SR-A in the lung is down-regulated. ②PMA can up- regulate the expression of SR-A on macrophage, that can accelerate the LPS endophage by macrophage and this effect can be inhibited by SR-A mAb(2F8). These observations suggested that SR-A may be related to the stagnation of LPS in the lung of mice with acute lung injury induced by LPS. ③During the course of ALI, the levels of TNF-αin the lung is increasing. Up-regulating the expression of SR-A on macrophage can decrease TNF-αproduce from macrophage, and this effect can be inhibited by SR-A mAb(2F8). These results suggested that the expression of SR-A may be related to the production of TNF-α.