HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print March 11, 2008

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0108016v1 83/6/1404    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Swee, M. Articles by Parks, W. C. Search for Related Content PubMed PubMed Citation Articles by Swee, M. Articles by Parks, W. C.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0108016

Received for publication January 9, 2008.
Revised February 13, 2008.
Accepted for publication February 14, 2008.

Article

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 ^*@

*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

^@ To whom correspondence should be addressed. E-mail: parksw{at}u.washington.edu.

	Abstract

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