Matrix metalloproteinase-7 (matrilysin) controls neutrophil egress by generating chemokine gradients.
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.
Swee
Mei
M
Center for Lung Biology and Institute for Stem Cell and Regenerative Medicine and Department of Medicine, University of Washington, Seattle, WA 98109, USA.
Wilson
Carole L
CL
Wang
Ying
Y
McGuire
John K
JK
Parks
William C
WC
D000818:Animals; D002465:Cell Movement; D018925:Chemokines / Q000096:biosynthesis*; D003092:Colitis / Q000276:immunology; D003106:Colon / Q000473:pathology; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis
D018925:Chemokines; D012333:RNA, Messenger; D009195:Peroxidase; D020783:Matrix Metalloproteinase 7