Overexpression of Alveolar Macrophage Gelatinase B (MMP-9) in Patients with Idiopathic Pulmonary Fibrosis
Autor: | Benoit Wallaert, Marie-Laure Franco-Montoya, Philippe Gosset, Alain Harf, Emmanuelle Lechapt-Zalcman, Hassan Lemjabbar, Chantal Lafuma |
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Rok vydání: | 1999 |
Předmět: |
Male
Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Pulmonary Fibrosis Blotting Western Clinical Biochemistry Matrix metalloproteinase Extracellular matrix Idiopathic pulmonary fibrosis Internal medicine Macrophages Alveolar medicine Humans Zymography Collagenases RNA Messenger Molecular Biology DNA Primers Microscopy Confocal Lung Base Sequence medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction business.industry Cell Biology Middle Aged respiratory system medicine.disease Immunohistochemistry respiratory tract diseases Bronchoalveolar lavage medicine.anatomical_structure Endocrinology Matrix Metalloproteinase 9 Alveolar macrophage Female Steroids business Immunosuppressive Agents |
Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 20:903-913 |
ISSN: | 1535-4989 1044-1549 |
Popis: | Alveolar macrophages (AM) express gelatinase B, a member of the matrix metalloproteinase family involved in the degradation and remodeling of extracellular matrix components. We evaluated the expression of gelatinase B in the course of idiopathic pulmonary fibrosis (IPF) by studying alveolar macrophages in culture AM and bronchoalveolar lavage fluid from 12 untreated patients with IPF, 11 patients with IPF under treatment with steroid and immunosuppressive agents, and 10 control subjects. By using zymography and quantitative image analysis, latent gelatinase B, as well an 88-kD active form, were investigated in culture medium (24 h) of AMs and were found to be significantly increased (P < 0.01) in untreated patients exhibiting severe IPF when compared with control subjects (4.1 +/- 1.7 versus 0.3 +/- 0.2 10(5) arbitrary units [AU]/10(4) AM for the 92-kD form). Concomitant studies of gelatinase B levels associated with cultured AM extracts or freshly harvested AM showed similar results, both at the mRNA and protein levels, respectively. Immunocytochemical studies on freshly harvested AM demonstrated that the enzyme was located mainly at the cell, suggesting some involvement of gelatinase B in AM migration. In contrast, gelatinase B activity secreted by AM tended to be normal in patients with IPF under steroid and immunosuppressive treatment. Simultaneously, level of the gelatinase B activity in epithelial lining fluid was increased in untreated IPF patients, whereas it was normal in treated patients. These results suggest that AM of patients with IPF are primed for gelatinase B expression and that steroid and immunosuppressive treatment induces negative modulation of the gelatinase B overexpression. We conclude that gelatinase B may play a role in lung remodeling in IPF. |
Databáze: | OpenAIRE |
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