Matrix metalloproteinase-7 (matrilysin) controls neutrophil egress by generating chemokine gradients Mei Swee * ,† , Carole L. Wilson ‡ , Ying Wang * ,† , John K. McGuire * ,† ,§ and William C. Parks * ,† ,1 * Center for Lung Biology and Institute for Stem Cell and Regenerative Medicine and Departments of † Medicine (Pulmonary and Critical Care Medicine), ‡ Pathology, and § Pediatrics (Critical Care Medicine), University of Washington, Seattle, Washington, USA 1 Correspondence: Center for Lung Biology, University of Washington, 815 Mercer Street, Seattle, WA 98109, USA. E-mail: parksw@u.washington.edu Matrilysin matrix metalloproteinase 7 (MMP7) is induced by mucosal injury of many tissues. To assess function of this proteinase, we subjected wild-type and Mmp7 –/– mice to acute colon injury. When matrilysin expression was increasing, 73% of wild-type mice died, whereas only 32% of Mmp7 –/– mice succumbed. Although re-epithelialization was delayed in Mmp7 –/– mice, overall injury did not differ markedly between genotypes. We hypothesized that differences in acute inflammation caused increased mortality in wild-type mice. Indeed, whereas overall neutrophil influx into tissue was similar in wild-type and Mmp7 –/– mice, their location and extent of migration differed between genotypes. Neutrophils were dispersed throughout the mucosa and within the lumen of wild-type mice, but these leukocytes were largely confined to the submucosa in Mmp7 –/– mice. The levels of neutrophil chemokines, keratinocyte-derived chemokine and MIP-2, increased in the colon tissue of both genotypes, but these factors were detected only in lumenal lavages of wild-type mice. Our findings indicate that matrilysin mediates beneficial and deleterious effects in response to injury. On one hand, it promotes re-epithelialization, but it also controls the transepithelial influx of neutrophils, which if excessive, can lead to tissue damage. Key Words: inflammation • epithelium • protease
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Matrix metalloproteinase-7 (matrilysin) controls neutrophil egress by generating chemokine gradients
Swee, Mei; Wilson, Carole L.; Wang, Ying; McGuire, John K.; Parks, William C.
Follow Journal of Leukocyte Biology
, Volume 83 (6): 1404
Fed of American Socs for Experimental Biology – Jun 1, 2008
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