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

为了研究其机制，我们在本研究中使用了通过将几种类型的坏死细胞注射到腹腔中诱导的炎症模型。注射坏死P388细胞（白血病细胞）和坏死腹膜中性粒细胞（坏死活化中性粒细胞）（在注射巯基乙酸盐肉汤后从腹膜腔获得）诱导中性粒细胞浸润，随后诱导单核细胞/巨噬细胞浸润，而注射坏死胸腺细胞和坏死骨髓中性粒细胞（坏死静息中性粒细胞）则不会。这些结果表明，坏死细胞诱导的炎症反应的诱导依赖于发生坏死的细胞类型。与细胞浸润的诱导一致，注射也诱导KC和MIP-2的产生，并且随后仅当注射坏死的P388细胞或坏死的活化的中性粒细胞时诱导MCP-1的产生。尽管KC的表达水平高于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浸润。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浸润中起重要作用。

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.