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

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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.