期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 83, 期 6, 页码 1404-1412出版社
WILEY
DOI: 10.1189/jlb.0108016
关键词
inflammation; epithelium; protease
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL073725, R01HL082658, K08HL068780, R01HL077555, P01HL029594] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK052574] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL 082658, HL 077555, HL 068780, K08 HL068780, R01 HL082658, R01 HL077555, P01 HL029594, HL 073725, HL 029594, R01 HL073725] Funding Source: Medline
- NIDDK NIH HHS [P30 DK052574, DK 52574] Funding Source: Medline
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.
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