Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice.

To determine which proteinases are responsible for the lung destruction characteristic of pulmonary emphysema, macrophage elastase-deficient (MME-/-) mice were subjected to cigarette smoke. In contrast to wild-type mice, MME-/- mice did not have increased numbers of macrophages in their lungs and did not develop emphysema in response to long-term exposure to cigarette smoke. Smoke-exposed MME-/- mice that received monthly intratracheal instillations of monocyte chemoattractant protein-1 showed accumulation of alveolar macrophages but did not develop air space enlargement. Thus, macrophage elastase is probably sufficient for the development of emphysema that results from chronic inhalation of cigarette smoke.

[1]  H. Chapman,et al.  The role of thiol proteases in tissue injury and remodeling. , 1994, American Journal of Respiratory and Critical Care Medicine.

[2]  S Gordon,et al.  Elastase secretion by stimulated macrophages. Characterization and regulation , 1975, The Journal of experimental medicine.

[3]  T. Ley,et al.  Molecular cloning, chromosomal localization, and bacterial expression of a murine macrophage metalloelastase. , 1992, The Journal of biological chemistry.

[4]  W. Thurlbeck,et al.  Scanning electronmicroscopic morphometry of emphysema in humans. , 1994, American journal of respiratory and critical care medicine.

[5]  M. Cosio,et al.  Alveolar inflammation and its relation to emphysema in smokers. , 1995, American journal of respiratory and critical care medicine.

[6]  A. Churg,et al.  Cigarette smoke causes physiologic and morphologic changes of emphysema in the guinea pig. , 1990, The American review of respiratory disease.

[7]  M. Feinleib,et al.  Trends in COPD morbidity and mortality in the United States. , 1989, The American review of respiratory disease.

[8]  D. Schwartz,et al.  Bronchoalveolar lavage cellularity. The distribution in normal volunteers. , 1992, The American review of respiratory disease.

[9]  R. Sandhaus,et al.  Experimental emphysema induced with purified human neutrophil elastase: tissue localization of the instilled protease. , 2015, The American review of respiratory disease.

[10]  J. Hoidal,et al.  Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters. , 1988, The Journal of clinical investigation.

[11]  Z. Werb,et al.  Mouse macrophage elastase. Purification and characterization as a metalloproteinase. , 1981, The Biochemical journal.

[12]  A. Eisen,et al.  Neutral metalloproteinases produced by human mononuclear phagocytes. Enzyme profile, regulation, and expression during cellular development. , 1990, The Journal of clinical investigation.

[13]  S. Shapiro,et al.  Human 92- and 72-kilodalton type IV collagenases are elastases. , 1991, The Journal of biological chemistry.

[14]  T. Ley,et al.  Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  S. Weiss,et al.  Interstitial collagenase (matrix metalloproteinase-1) expresses serpinase activity. , 1991, The Journal of clinical investigation.

[16]  C. Laurell,et al.  The Electrophoretic α;1-Globulin Pattern of Serum in α;1-Antitrypsin Deficiency , 1963 .

[17]  S. Shapiro,et al.  Human Macrophage Metalloelastase. GENOMIC ORGANIZATION, CHROMOSOMAL LOCATION, GENE LINKAGE, AND TISSUE-SPECIFIC EXPRESSION (*) , 1995, The Journal of Biological Chemistry.

[18]  D. Niewoehner,et al.  Pathologic changes in the peripheral airways of young cigarette smokers. , 1974, The New England journal of medicine.

[19]  R. Senior,et al.  Matrilysin is much more efficient than other matrix metalloproteinases in the proteolytic inactivation of alpha 1-antitrypsin. , 1994, Biochemical and biophysical research communications.

[20]  M. Dunnill.  Quantitative Methods in the Study of Pulmonary Pathology , 1962, Thorax.

[21]  G. Snider,et al.  Emphysema: the first two centuries--and beyond. A historical overview, with suggestions for future research: Part 1. , 1992, The American review of respiratory disease.