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 and phlogistins using a modified murine in vivo sponge model in which gelatin sponges are soaked with chemoattractant and implanted in the peritoneal cavity. 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 macrophages 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 administration of methotrexate, piroxicam or dexamethasone, and JE/MCP-1-mediated trafficking was impaired by treatment with anti-JE antibody or with IL-10, suggesting a role for pro-inflammatory factors in amplifying the JE/MCP-1-induced response. This amplification phase involves the production of the chemokine KC, since anti-KC antibody significantly attenuated JE/MCP-1-induced chemotaxis. These results indicate that intraperitoneally implanted chemoattractant-soaked gelatin sponges are capable of inducing a pronounced inflammatory response characterized by the selective migration of leukocyte populations, and suggest that this model may be useful for delineating the activity of novel inhibitors of leukocyte chemotaxis.
Fine
J S
JS
Department of Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Jackson
J V
JV
Rojas-Triana
A
A
Bober
L A
LA
D000818:Animals; D018932:Chemokine CCL2 / Q000494:pharmacology; D018925:Chemokines / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D015503:Surgical Sponges; D015054:Zymosan / Q000494:pharmacology
D018932:Chemokine CCL2; D018925:Chemokines; D015054:Zymosan