Dale K. Kobayashi

TL;DR: 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, indicating that macrophage elastase is probably sufficient for the development of emphysema that results from chronic inhalation of cigarette smoke.

TL;DR: HME is a unique human metalloproteinase that possesses elastolytic activity and is expressed in alveolar macrophages; it is therefore a candidate molecule for the causation of diseases characterized by damage to the extracellular matrix.

TL;DR: A direct role for neutrophil elastase in emphysema is demonstrated and the interdependence of the proteinases and inflammatory cells that mediate lung destruction in response to cigarette smoke is highlighted.

TL;DR: It is demonstrated that purified murine and human matrix metalloproteinases generate biologically functional angiostatin from plasminogen by employing macrophages isolated from MME-deficient mice and their wild-type littermates to demonstrate that MME is required for the generation of angiOSTatin that inhibits the proliferation of human microvascular endothelial cells.

TL;DR: Elastin fragment antagonism in this model abrogated both macrophage accumulation and airspace enlargement and an mAb against elastin fragments eliminated both the in vitro chemotactic activity and cigarette smoke-induced monocyte recruitment to the lung in vivo.