| First Author | Albaiceta GM | Year | 2010 |
| Journal | Am J Respir Cell Mol Biol | Volume | 43 |
| Issue | 5 | Pages | 555-63 |
| PubMed ID | 19995943 | Mgi Jnum | J:177811 |
| Mgi Id | MGI:5296301 | Doi | 10.1165/rcmb.2009-0034OC |
| Citation | Albaiceta GM, et al. (2010) Absence or inhibition of matrix metalloproteinase-8 decreases ventilator-induced lung injury. Am J Respir Cell Mol Biol 43(5):555-63 |
| abstractText | Mechanical ventilation is a life-saving therapy that can also damage the lungs. Ventilator-induced lung injury (VILI) promotes inflammation and up-regulates matrix metalloproteinases (MMPs). Among these enzymes, MMP-8 is involved in the onset of inflammation by processing different immune mediators. To clarify the role of MMP-8 in a model of VILI and their relevance as a therapeutic target, we ventilated wild-type and MMP-8-deficient mice with low or high pressures for 2 hours. There were no significant differences after low-pressure ventilation between wild-type and knockout animals. However, lack of MMP-8 results in better gas exchange, decreased lung edema and permeability, and diminished histological injury after high-pressure ventilation. Mmp8(-/-) mice had a different immune response to injurious ventilation, with decreased neutrophilic infiltration, lower levels of IFN-gamma and chemokines (LPS-induced CXC chemokine, macrophage inflammatory protein-2), and significant increases in anti-inflammatory cytokines (IL-4, IL-10) in lung tissue and bronchoalveolar lavage fluid. There were no differences in MMP-2, MMP-9, or tissue inhibitor of metalloproteinase-1 between wild-type and knockout mice. These results were confirmed by showing a similar protective effect in wild-type mice treated with a selective MMP-8 inhibitor. We conclude that MMP-8 promotes acute inflammation after ventilation with high pressures, and its short-term inhibition could be a therapeutic goal to limit VILI. |
