Swee Mei, Wilson Carole L, Wang Ying, McGuire John K, Parks William C
Center for Lung Biology and Institute for Stem Cell and Regenerative Medicine and Department of Medicine, University of Washington, Seattle, WA 98109, USA.
J Leukoc Biol. 2008 Jun;83(6):1404-12. doi: 10.1189/jlb.0108016. Epub 2008 Mar 11.
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.
基质溶素[基质金属蛋白酶7（MMP7）]由多种组织的黏膜损伤诱导产生。为评估这种蛋白酶的功能，我们对野生型和Mmp7基因敲除小鼠进行了急性结肠损伤实验。当基质溶素表达增加时，73%的野生型小鼠死亡，而只有32%的Mmp7基因敲除小鼠死亡。虽然Mmp7基因敲除小鼠的上皮再形成延迟，但两种基因型小鼠的总体损伤并无明显差异。我们推测，急性炎症的差异导致野生型小鼠死亡率增加。实际上，虽然野生型和Mmp7基因敲除小鼠中进入组织的中性粒细胞总数相似，但不同基因型小鼠中性粒细胞的位置和迁移范围有所不同。野生型小鼠的中性粒细胞分散在整个黏膜及管腔内，但在Mmp7基因敲除小鼠中，这些白细胞主要局限于黏膜下层。两种基因型小鼠结肠组织中中性粒细胞趋化因子、角质形成细胞衍生趋化因子和MIP-2的水平均升高，但这些因子仅在野生型小鼠的管腔灌洗液中检测到。我们的研究结果表明，基质溶素在损伤反应中介导了有益和有害的作用。一方面，它促进上皮再形成，但它也控制中性粒细胞的跨上皮流入，而中性粒细胞流入过多会导致组织损伤。
