Macrophage inflammatory protein-2 is required for neutrophil passage across the epithelial barrier of the infected urinary tract

IL-8 is a major human neutrophil chemoattractant at mucosal infection sites . This study examined the C-X-C chemokine response to mucosal infection, an d, specifically, the role of macrophage inflammatory protein (MIP)-2, one o f the mouse IL-8 equivalents, for neutrophil-epithelial interactions. Follo wing intravesical Escherichia coli infection, several C-X-C chemokines were secreted into the urine, but only MIP-2 concentrations correlated to neutr ophil numbers. Tissue quantitation demonstrated that kidney MIP-2 productio n was triggered by infection, and immunohistochemistry identified the kidne y epithelium as a main source of MIP-2. Treatment with anti-MIP-2 Ab reduce d the urine neutrophil numbers, but the mice had normal tissue neutrophil l evels. By immunohistochemistry, the neutrophils were found in aggregates un der the pelvic epithelium, but in control mice the neutrophils crossed the urothelium into the urine. The results demonstrate that different chemokine s direct neutrophil migration from the bloodstream to the lamina propria an d across the epithelium and that MIP-2 serves the latter function. These fi ndings suggest that neutrophils cross epithelial cell barriers in a highly regulated manner in response to chemokines elaborated at this site. This is yet another mechanism that defines the mucosal compartment and differentia tes the local from the systemic host response.