Matrix metalloproteinase‐1 (interstitial collagenase) and matrix metalloproteinase‐3 promote disease progression in acute lung injury

In the studies reported here, we obtained bronchoalveolar lavage (BAL) fluid from individuals with acute lung inflammation (ALI) or acute respiratory distress syndrome (ARDS). Specimens were examined for expression of MMP‐1 (interstitial collagenase), MMP‐2 (gelatinase A), MMP‐3 (stromelysin‐1), MMP‐8 (neutrophil collagenase) and MMP‐9 (gelatinase B) as well as TIMP‐1 (tissue inhibitor of metalloproteinase‐1). In nearly all specimens, there were high levels of MMP‐2, MMP‐8, MMP‐9 and TIMP‐1, but in only a subset of patients were there detectable levels of MMP‐1 and/or MMP‐3. In the patients with elevated MMP‐1 and/or MMP‐3, disease severity and mortality rate was higher than in the group without detectable levels of these enzymes. In parallel studies, mice lacking MMP‐1 and MMP‐3 were subjected to immune complex‐induced acute lung injury in the presence or absence of exogenous MMP‐1 and/or MMP‐3. Animals without MMP‐1 or MMP‐3 developed a mild, self‐limited alveolitis. In contrast, mice with MMP‐1 and MMP‐3 developed a much more severe alveolitis in which destruction of the alveolar wall was apparent in places. Based on these findings, we conclude that elevated MMP‐2, MMP‐8 and MMP‐9 in BAL fluid is a marker of acute lung inflammation while detectable MMP‐1 and/or MMP‐3 is related to disease progression.