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.
Hautamaki
R D
RD
Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO 63110, USA.
Kobayashi
D K
DK
Senior
R M
RM
Shapiro
S D
SD
D000818:Animals; D002452:Cell Count; D018932:Chemokine CCL2 / Q000494:pharmacology; D018390:Gene Targeting; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000201:enzymology* / Q000502:physiology; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009504:Neutrophils; D010947:Plants, Toxic; D011650:Pulmonary Alveoli / Q000473:pathology; D011656:Pulmonary Emphysema / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects*; D014026:Nicotiana
D018932:Chemokine CCL2; D012906:Smoke; D008666:Metalloendopeptidases; D053508:Matrix Metalloproteinase 12