A Disintegrin and A Metalloproteinase-9 (ADAM9): A Novel Proteinase Culprit with Multifarious Contributions to COPD.

Introduction: Proteinases with a disintegrin and a metalloproteinase domain (ADAMs) have not been well studied in COPD. We investigated whether ADAM9 is linked to COPD in humans and mice.

Methods: ADAM9 blood and lung levels were measured in COPD patients versus controls, and air- versus cigarette smoke (CS)-exposed wild-type (WT) mice.

The role of the CCR1 receptor in the inflammatory response to tobacco smoke in a mouse model.

Objective: The aim was to create pathological changes in mice relevant to human smoke exposure that can be used to further understand the mechanisms and pathology of smoke-induced inflammatory disease.

Methods: Mice were exposed to tobacco smoke or lipopolysaccharide (LPS) to generate an inflammatory infiltrate within the lungs.

Results: Tobacco smoke exposure over a 4 day period led to neutrophilia in the lungs of BALB/c mice.

TNF-alpha-induced self expression in human lung endothelial cells is inhibited by native and oxidized alpha1-antitrypsin.

Endothelial cells are among the main physiological targets of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). In endothelial cells TNF-alpha elicits a broad spectrum of biological effects including differentiation, proliferation and apoptosis. alpha1-antitrypsin (AAT), an endogenous inhibitor of serine proteases plays a vital role in protecting host tissue from proteolytic injury at sites of inflammation.

Expression of genes involved in oxidative stress responses in airway epithelial cells of smokers with chronic obstructive pulmonary disease.

Rationale: The molecular mechanisms involved in airway oxidative stress responses reported in healthy smokers and in those with chronic obstructive pulmonary disease (COPD) are poorly understood.

Objectives: To assess the expression of genes involved in oxidative stress responses in the bronchial epithelium of smokers with or without COPD and in relation to disease severity.

Methods: Global gene expression was assessed in bronchial brushings in 38 subjects with COPD, 14 healthy nonsmokers, and 18 healthy smokers.

Inhibition of lipopolysaccharide-mediated human monocyte activation, in vitro, by alpha1-antitrypsin.

alpha1-Antitrypsin (AAT) is a major circulating and tissue inhibitor of serine proteinases. As such AAT is thought to play an important role in limiting host tissue injury at sites of inflammation. There is now increasing evidence, however, that AAT may exhibit biological activity independent of its protease inhibitor function.