Pulmonary retention of PMN attracts primed intestinal lymphocytes in a mouse model of inflammatory bowel disease.

Abstract

Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal (GI) tract. IBD is also associated with a number of co-morbidities that can include inflammation in the lung (Black et al. Chest 2007). IBD-induced pulmonary inflammation is characterized by polymorphonuclear neutrophil (PMN) and lymphocyte inflammation. We have demonstrated neutrophilia and an increase in PMN in the pulmonary system in the DSS model of colitis. We hypothesized that colitis induces PMN-mediated inflammation in the lung, which attracts GI-primed lymphocytes. Employing the DSS model of colitis, we observed a significant correlation between PMN in the circulatory and pulmonary system (R2=0.845, N=12). Extravasation of PMN into lung tissue was observed and was associated with a 2-fold increase in integrin β2 expression and an increase in IL-1β and CCL2 protein levels. To examine whether DSS pulmonary inflammation resulted in lymphocyte recruitment to the lungs, an adoptive transfer experiment was performed. Lymphocytes isolated from the mesenteric lymph nodes (MLN) of donor mice (DSS & controls) were CFSE-stained and transferred i.v. into recipient mice (DSS & controls). The distribution of these cells in the spleen, lung, colon and MLN was measured by FACS. There was a significant increase in lymphocytes in the lungs of mice receiving donor cells from colitis, but not healthy mice (P=0.0429, N=6). These data suggest that GI inflammation leads to pooling of PMN in the pulmonary system, which drives lymphocyte mishoming to the lung. These cells may mediate the subsequent pulmonary manifestations of IBD and offer a model to further investigate inflammatory organ cross-talk.