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Clinical Investigations: COPD |

Upregulation of Gelatinases A and B, Collagenases 1 and 2, and Increased Parenchymal Cell Death in COPD*

Lourdes Segura-Valdez, PhD; Annie Pardo, PhD; Miguel Gaxiola, MD; Bruce D. Uhal, PhD; Carina Becerril, MSc; Moisés Selman, MD, FCCP
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*From the Instituto Nacional de Enfermedades Respiratorias (Drs. Segura-Valdez, Gaxiola, Selman, and Ms. Becerril), Mexico City, Mexico; Michael Reese Hospital (Dr. Uhal), University of Illinois, Chicago, IL; and Facultad de Ciencias, Universidad Nacional Autónoma de México (Dr. Pardo), Mexico City, Mexico.

Correspondence to: Moisés Selman, MD, FCCP, Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502; Col. Sección XVI, México DF, CP 14080, México; e-mail: mselman@mailer.main.conacyt.mx



Chest. 2000;117(3):684-694. doi:10.1378/chest.117.3.684
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Background: A central feature in the pathogenesis of COPD is the inflammation coexisting with an abnormal protease/antiprotease balance. However, the possible role of different serine and metalloproteinases remains controversial.

Patients and measurements: We examined the expression of gelatinases A and B (matrix metalloproteinase [MMP]-2 and MMP-9); collagenases 1, 2, and 3 (MMP-1, MMP-8, and MMP-13); as well as the presence of apoptosis in lung tissues of 10 COPD patients and 5 control subjects. In addition, gelatinase-A and gelatinase-B activities were assessed in BAL obtained from eight COPD patients, and from six healthy nonsmokers and six healthy smoker control subjects.

Setting: Tertiary referral center and university laboratories of biochemistry, and lung cell kinetics.

Results: Immunohistochemical analysis of COPD lungs showed a markedly increased expression of collagenases 1 and 2, and gelatinases A and B, while collagenase 3 was not found. Neutrophils exhibited a positive signal for collagenase 2 and gelatinase B, whereas collagenase 1 and gelatinase A were revealed mainly in macrophages and epithelial cells. BAL gelatin zymography showed a moderate increase of progelatinase-A activity and intense bands corresponding to progelatinase B. In situ end labeling of fragmented DNA displayed foci of positive endothelial cells, although some alveolar epithelial, interstitial, and inflammatory cells also revealed intranuclear staining.

Conclusion: These findings suggest that there is an upregulation of collagenase 1 and 2 and gelatinases A and B, and an increase in endothelial and epithelial cell death, which may contribute to the pathogenesis of COPD through the remodeling of airways and alveolar structures.

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