Collagen-binding integrin α1β1 regulates intestinal inflammation in experimental colitis

Abstract

Central to inflammatory responses are the integrin-mediated adhesive interactions of cells with their ECM-rich environment. We investigated the role of the collagen-binding integrin 1 1 in intestinal inflammation using the mouse model of colitis induced by dextran sodium sulfate (DSS). mAb's directed against murine 1 were found to significantly attenuate inflammation and injury in DSS-treated wild-type mice; similar protection was seen in mice deficient for 1 1 integrin. Blockade or loss of 1 1 was also associated with decreased mucosal inflammatory cell infiltrate and cytokine production. Importantly, we demonstrated that development and 1 -mediated inhibition of DSS-induced colitis occurred independently of lymphocytes (Rag-2 -/-mice), and identified the monocyte as a key 1 1 -expressing cell type involved in the development of colitis in this model. In response to DSS, both 1 deficiency and anti- 1 mAb treatment significantly reduced monocyte accumulation and activation within the lamina propria. In summary, the data demonstrate that engagement of leukocyte-associated 1 1 receptors with ECM plays a pivotal role in mediating intestinal inflammation via promotion of monocyte movement and/or activation within the inflamed interstitium. Therapeutic strategies designed to disrupt such interactions may prove beneficial in treating intestinal inflammation.