357. IL-17 Induces Migration of Adult Marrow Stromal Cells to Lung Epithelium

Abstract

Recent studies demonstrate that adult bone marrow-derived cells can be recruited to lung and undergo phenotypic conversion to lung epithelial and interstitial cells. The mechanisms by which this occurs are unknown. We postulated that lung epithelium releases soluble mediators with the capacity to recruit marrow-derived stromal cells. To test this, primary murine tracheal epithelial cells (MTEC) were cultured on a supported semi-permeable membrane (Transwell) under air-liquid interface conditions. When cells developed tight junctions, stromal marrow cells derived from adult transgenic GFP-expressing mice, cultured on glass cover slips, were placed in the lower Transwell chamber. After 1 week, a small number of stromal cells were observed to have migrated to the permeable membrane. The number of migrating cells substantially increased after MTEC were stimulated with endotoxin (25 |[mu]|g/well, 1 hr). Media from na|[iuml]|ve and endotoxin-stimulated MTEC and from the stromal marrow cells were assayed for multiple chemokines. Stromal-derived factor (SDF-1), a chemokine implicated in stem cell mobilization was produced in higher amounts by stromal cells than by MTEC (908 vs 100 pg/ml), suggesting that SDF-1 release by epithelial cells may not drive stromal cell migration in the lung. In contrast, IL-17 was released in higher amounts by both na|[iuml]|ve and endotoxin-stimulated MTEC than by stromal cells. Adding neutralizing anti IL-17 antibody (1 |[mu]|g/ml) to the culture media blocked migration of stromal cells to the transwell membrane. These data provide a functional model for assay of airway epithelial cell-marrow derived stromal cell interactions that are important for repair in lung injury and implicate a critical role of IL-17 in migration of adult marrow-derived stromal cells to lung epithelium.