| First Author | Kim KH | Year | 2005 |
| Journal | Am J Respir Cell Mol Biol | Volume | 33 |
| Issue | 3 | Pages | 271-9 |
| PubMed ID | 15947421 | Mgi Jnum | J:112941 |
| Mgi Id | MGI:3664010 | Doi | 10.1165/rcmb.2005-0111OC |
| Citation | Kim KH, et al. (2005) Tissue inhibitor of metalloproteinase-1 deficiency amplifies acute lung injury in bleomycin-exposed mice. Am J Respir Cell Mol Biol 33(3):271-9 |
| abstractText | Bleomycin-induced lung injury triggers a profound and durable increase in tissue inhibitor of metalloproteinase (TIMP)-1 expression, suggesting a potential role for this antiproteinase in the regulation of lung inflammation and fibrosis. TIMP-1 protein induction is spatially restricted to areas of lung injury as determined by immunohistochemistry. Using TIMP-1 null mutation mice, we demonstrate that TIMP-1 deficiency amplifies acute lung injury as determined by exaggerated pulmonary neutrophilia, hemorrhage, and vascular permeability compared with wild-type littermates after bleomycin exposure. The augmented pulmonary neutrophilia observed in TIMP-1-deficient animals was not found in similarly treated TIMP-2-deficient mice. Using TIMP-1 bone marrow (BM) chimeric mice, we observed that the TIMP-1-deficient phenotype was abolished in wild-type recipients of TIMP-1-deficient BM but not in TIMP-1-deficient recipients of wild-type BM. Acute lung injury in TIMP-1-deficient mice was accompanied by exaggerated gelatinase-B activity in the alveolar compartment. TIMP-1 deficiency did not alter neutrophil chemotactic factor accumulation in the injured lung nor neutrophil migration in response to chemotactic stimuli in vivo or in vitro. Moreover, TIMP-1 deficiency did not modify collagen accumulation after bleomycin injury. Our results provide direct evidence that TIMP-1 contributes significantly to the regulation of acute lung injury, functioning to limit inflammation and lung permeability. |
