Requirement for Macrophage Elastase for Cigarette Smoke-Induced Emphysema in Mice
R. Dean Hautamaki,
Dale K. Kobayashi,
Robert M. Senior,
Steven D. Shapiro
*
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.
Departments of Internal Medicine, and Cell Biology and Physiology,
Washington University School of Medicine at Barnes-Jewish Hospital, St.
Louis, MO 63110, USA.
*
To whom correspondence should be addressed. E-mail:
sshapiro{at}imgate.wustl.edu
