• Guillermo M Albaiceta, Ana Gutierrez-Fernández, Emilio García-Prieto, Xose S Puente, Diego Parra, Aurora Astudillo, Cristina Campestre, Sandra Cabrera, Adrian Gonzalez-Lopez, Antonio Fueyo, Francisco Taboada, and Carlos López-Otin.
• Department of Biología Funcional, Universidad de Oviedo, Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain. guillermo.muniz@sespa.princast.es
• Am. J. Respir. Cell Mol. Biol. 2010 Nov 1;43(5):555-63.

AbstractMechanical 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-γ 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.

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