Role of matrix metalloproteinases in models of macrophage-dependent acute lung injury: evidence for alveolar macrophage as source of proteinases

DF Gibbs, TP Shanley, RL Warner… - American journal of …, 1999 - atsjournals.org
DF Gibbs, TP Shanley, RL Warner, HS Murphy, J Varani, KJ Johnson
American journal of respiratory cell and molecular biology, 1999atsjournals.org
Matrix metalloproteinases (MMPs) have been implicated in the tissue injury seen in
neutrophil-dependent models of acute lung injury. However, the role of MMPs in
macrophage-dependent models of lung injury is unknown. To address this issue, the
macrophage-dependent immunoglobulin A immune complex–induced lung injury model
and the macrophage-dependent portion of the lipopolysaccharide-induced acute lung injury
model in the rat were assessed for MMP involvement and for the source of these activities. In …
Matrix metalloproteinases (MMPs) have been implicated in the tissue injury seen in neutrophil-dependent models of acute lung injury. However, the role of MMPs in macrophage-dependent models of lung injury is unknown. To address this issue, the macrophage-dependent immunoglobulin A immune complex–induced lung injury model and the macrophage-dependent portion of the lipopolysaccharide-induced acute lung injury model in the rat were assessed for MMP involvement and for the source of these activities. In both models, injury was inhibited by the recombinant human tissue inhibitor of metalloproteinases-2. Bronchoalveolar lavage fluids (BALFs) from injured animals in both models showed increased levels of MMPs. Characterization of MMP production by isolated lung fibroblasts, endothelial cells, type II epithelial cells, and alveolar macrophages revealed that only the macrophage had the same spectrum of MMP activity as seen in the BALF. Further, isolated alveolar macrophages from injured lungs showed evidence of in vivo activation with the release of the same spectrum of MMP activities. Together these studies show that MMPs are produced during macrophage-dependent lung injury, that these MMPs play a role in the development of the lung injury, and that the alveolar macrophage is the likely source of these MMPs.
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