Involvement of KC, MIP-2, and MCP-1 in leukocyte infiltration following injection of necrotic cells into the peritoneal cavity

Although necrotic cells are known to induce inflammation in vivo, the underlying mechanism remains largely unexplored. In order to examine the mechanism, we used an inflammation model induced by injection of necrotic leukemic P388 cells into the peritoneal cavity in this study. The injection of necrotic cells induced the infiltration of neutrophils and subsequently that of monocytes/macrophages. In agreement with this, the injection also induced the production of KC and MIP-2, and subsequently that of MCP-1. 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. Antibodies against CXCR2, a sole receptor for KC and MIP-2, almost completely inhibited the infiltration of neutrophils and monocytes/macrophages. Anti-MCP-1 Ab, on the other hand, inhibited the infiltration of monocytes/macrophages but not 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 and that neutrophils may regulate monocyte/macrophage infiltration in our model.