MIP-2 secreted by epithelial cells increases neutrophil and lymphocyte recruitment in the mouse intestine

Background-Invasion of the intestinal mucosa by leucocytes is a characteris tic of intestinal inflammation but the role of the epithelium in orchestrat ing this recruitment has not been examined in vivo. Cultured intestinal epi thelial cells secrete a wide variety of chemokines, often in response to ag ents present in the intestinal lumen. Macrophage inflammatory protein 2 (MI P-2) is a chemokine that attracts neutrophils, and its secretion from intes tinal epithelial cells is enhanced by inflammatory stimuli such as interleu kin 1 beta. We hypothesised that the production of MIP-2 by epithelial cell s would increase leucocyte migration into the intestine. Aim-To study the effects of a chemokine secreted from intestinal epithelial cells in vivo. Methods-MIP-2 was expressed in the mouse intestinal epithelium using an epi thelial cell specific promoter from the gene encoding the intestinal fatty acid binding protein. The intestines of these transgenic mice were then ana lysed. Results-Epithelial cells from transgenic mice expressed MIP-2 but wild-type mice did not. Neutrophil recruitment, examined by myeloperoxidase (MPO) st aining and total MPO activity per unit weight of intestine, was significant ly increased in transgenic mice in both the small intestine and proximal co lon, and this was blocked by anti-MIP-2 antibody treatment. Both intraepith elial and lamina propria lymphocytes were also increased in transgenic mice . They showed chemotactic activity to MIP-2 in the Boyden chambers and expr essed MIP-2 receptor (CXCR-2) mRNA confirmed by reverse transcription-polym erase chain reaction. Conclusion-These experiments are the first to show a functional role for ep ithelial chemokines in vivo and reveal an unexpected role for the neutrophi l chemokine MIP-2 in controlling mucosal lymphocyte migration.