Increase of matrix metalloproteinases in woodsmoke-induced lung emphysema in guinea pigs.
Elastolysis, collagenolysis and gelatinolysis are essential in the pathogenesis of tobacco smoke-induced emphysema; however, these activities have been scantily studied in emphysema secondary to woodsmoke. The aim of this study was to analyze elastolysis, collagenolysis and gelatinolysis, MMP-1, MMP-2, and MMP-9 expression, and apoptosis in guinea pigs exposed to smoke produced by 60 g/day of pine wood, 5 days/week, from 1 to 7 months. Histological analysis after 4 to 7 months in smoke exposed guinea pigs showed alveolar mononuclear phagocyte and lymphocytic peribronchiolar inflammation, epithelial and smooth muscle hyperplasia, and pulmonary arterial hypertension. Mild to moderate emphysematous lesions were observed in woodsmoke-exposed animals at 4 to 7 months by increase of mean linear intercepts. A higher percentage of whole blood carboxyhemoglobin (COHb) and elastolytic activity in bronchoalveolar lavage macrophages and lung tissue homogenates was observed at all times. Collagenolysis was increased after 4 to 7 months in woodsmoke-exposed animals, although collagen concentration did not change. Zymography revealed increase in lysis bands of the active MMP-2 and MMP-9 at 4 and 7 months in bronchoalveolar lavage fluid and lung tissue homogenate. Positive immunostaining for MMP-1 and MMP-9 was observed in epithelial cells and macrophages in wood exposed animals at 4 to 7 months. Real-time PCR showed MMP-2 and MMP-9 expression at 3 to 7 months in exposed animals. Furthermore, apoptosis was increased at all times in bronchoalveolar lavage macrophages and lung tissue from exposed animals. Results support a role of metalloproteinases and apoptosis in emphysema secondary to woodsmoke exposure.
Departamento de Investigación en Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico. cramosa@prodigy.net.mx
Carlos
C
Ramos
Jose
J
Cisneros
Georgina
G
Gonzalez-Avila
Carina
C
Becerril
Víctor
V
Ruiz
Martha
M
Montaño
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002263:Carboxyhemoglobin / Q000032:analysis; D002452:Cell Count; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D006168:Guinea Pigs; D007150:Immunohistochemistry; D019570:Inhalation Exposure / Q000009:adverse effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D011656:Pulmonary Emphysema / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke / Q000009:adverse effects*; D013997:Time Factors; D014934:Wood
D052638:Particulate Matter; D012906:Smoke; D005780:Gelatin; D003094:Collagen; D004549:Elastin; D002263:Carboxyhemoglobin; D020782:Matrix Metalloproteinases