Evaluation of chemokine- and phlogistin-mediated leukocyte chemotaxis using an in vivo sponge model

We have directly compared the in vivo activity of a number of chemokines an d phlogistins using a modified murine in vivo sponge model in which gelatin sponges are soaked with chemoattractant and implanted in the peritoneal ca vity. Sponges soaked with murine JE/MCP-1 (monocyte chemoattractant protein -1) or zymosan promoted the chemotaxis of specific leukocyte populations in a time-dependent manner, as judged by multiparameter flow cytometry, with granulocytes predominating in zymosan-soaked sponges and granulocytes and m acrophages present in JE/MCP-1-soaked sponges. Smaller numbers of B, T and dendritic cells were identified as well. Eotaxin selectively chemoattracted eosinophils in this model, while MIG induced significant T cell migration relative to other chemokines. Cell migration was inhibited by administratio n of methotrexate, piroxicam or dexamethasone, and JE/MCP-1-mediated traffi cking was impaired by treatment with anti-JE antibody or with IL-10, sugges ting a role for pro-inflammatory factors in amplifying the JE/MCP-1-induced response. This amplification phase involves the production of the chemokin e KC, since anti-KC antibody significantly attenuated JE/MCP-1-induced chem otaxis. These results indicate that intraperitoneally implanted chemoattrac tant-soaked gelatin sponges are capable of inducing a pronounced inflammato ry response characterized by the selective migration of leukocyte populatio ns, and suggest that this model may be useful for delineating the activity of novel inhibitors of leukocyte chemotaxis.