The role of DAMPs on induction and termination of inflammatory responses induced by necrotic cells.

在本研究中，我们使用了一种通过向腹膜腔内注射几种类型的坏死性细胞而诱导的炎症模型来研究其机制。注射坏死性P388细胞(白血病细胞)和腹膜坏死性中性粒细胞(坏死性激活的中性粒细胞)，可诱导中性粒细胞和随后的单核/巨噬细胞的渗透，而注射坏死性胸腺细胞和坏死性骨髓中性粒细胞(坏死性静止性中性粒细胞)则不能。这些结果表明，坏死细胞诱导的炎症反应依赖于发生坏死的细胞类型。与诱导细胞浸润相一致，注射也可诱导KC和MIP-2的产生，随后只有在注射坏死性P388细胞或坏死性激活的中性粒细胞时才能诱导MCP-1的产生。尽管KC水平高于MIP-2，但抗KC抗体和抗MIP-2抗体均能显著抑制中性粒细胞的渗入。这些结果表明，KC和MIP-2在中性粒细胞向坏死细胞注射部位的渗透中起重要作用。

In order to examine the mechanism, we used an inflammation model induced by injection of several types of necrotic cells into the peritoneal cavity in this study. The injection of necrotic P388 cells(leukemia cells) and necrotic peritoneal neutrophils(necrotic activated neutrophils), which were obtained from the peritoneal cavity upon injection of thioglycollate broth, induced the infiltration of neutrophils and subsequently that of monocytes/macrophages, whereas the injection of necrotic thymocytes and necrotic bone marrow neutrophils(necrotic resting neutrophils) did not. These results suggested that the induction of inflammatory response induced by necrotic cells depend on the cell type undergoing necrosis. In agreement with induction of cell infiltration, the injection also induced the production of KC and MIP-2, and subsequently that of MCP-1 only when necrotic P388 cells or necrotic activated neutrophils were injected. Although the level of KC was higher than that of MIP-2, both anti-KC Ab and anti-MIP-2 Ab significantly inhibited the infiltration of neutrophils. These results indicate that KC and MIP-2 play important roles in the infiltration of neutrophils into the site of injection of necrotic cells.