HIGHER CONCENTRATIONS OF MATRIX METALLOPROTEINASES IN BRONCHOALVEOLARLAVAGE FLUID OF PATIENTS WITH ADULT-RESPIRATORY-DISTRESS-SYNDROME

This study was designed to investigate possible involvement of type IV collagenolytic matrix metalloproteinases (MMPs; 72-kDa type IV collag enase [MMP-2], 92-kDa type IV collagenase [MMP-9]), and the respective specific tissue inhibitors of these MMPs (TIMP-2 and TIMP-1) in the d evelopment of adult respiratory distress syndrome (ARDS). We determine d the concentrations of these enzymes in the bronchoalveolar ravage fl uid (BALF) from patients with ARDS using newly developed sensitive one -step sandwich enzyme immunoassay methods. BALF obtained from the 17 p atients and eight healthy volunteer control subjects were also used fo r the analysis of the number of the cellular component. Concentrations of the 7S portion of type IV collagen and laminin in the BALF were me asured as markers of basement membrane disruption. In the BALF from th e ARDS patients, the concentrations of MMP-2 (66.7 +/- 57.0 ng/ml vers us < 7.0 ng/ml for controls, p < 0.01) and MMP-9 (118.0 +/- 309.3 ng/m l versus 9.0 +/- 9.5 ng/ml for controls, p < 0.05), and the specific i nhibitor of MMP-9 (TIMP-1) (161.0 +/- 145.0 ng/ml versus < 50 ng/ml fo r controls, p < 0.01) were significantly higher compared with those fo r healthy control subjects. In the ARDS patients, the concentrations o f MMP-2 correlated both with those of 7S collagen and laminin; MMP-9 w ith the concentration of 7S collagen and the number of neutrophils. Th ese findings suggest that the increased concentration of collagenolyti c MMPs in lung plays role in the pathogenesis of ARDS.