The respiratory manifestations of cystic fibrosis (CF) are characterized by neutrophil-dominated airway inflammation. Since a variety of inflammatory stimuli are capable of inducing bronchial epithelial cells to express the gene for IL-8, a cytokine that attracts and activates neutrophils, mediators in respiratory epithelial lining fluid (ELF) of CF individuals might induce IL-8 production by e...

Expression of the PML-retinoic acid receptor (PML-RAR ) fusion protein is the initiating genetic event for acute promyelocytic leukemia (APL), but the molecular mechanisms responsible for disease initiation are not yet clear. Several observations have suggested that early myeloid cells are uniquely susceptible to transformation by PML-RAR . Recently, we have shown that the early myeloid-specifi...

Activated neutrophils use myeloperoxidase (MPO) to generate an array of potent toxic oxidants. In the current studies we used genetically altered mice deficient in MPO to investigate the role of the enzyme in host defense against the Gram-negative bacterium Klebsiella pneumoniae, an important human pathogen. For comparison, we used mice deficient in the antimicrobial molecule, neutrophil elasta...

Airway occlusion by mucus in chronic obstructive disease (COPD) is associated with a poor prognosis. We hypothesised that tiotropium has the ability to inhibit neutrophil elastase (NE)-induced goblet cell metaplasia in mice and mucin production in vitro. On days 1, 4, and 7, tiotropium or vehicle was administered to C57BL/6 mice by inhalation and they were allowed to intranasally aspirate human...

STUDY OBJECTIVES Pre-elafin, also known as trappin-2, is an elastase-specific inhibitor that could be an ideal candidate for the treatment of neutrophil elastase-driven lung diseases. The inhibitory activity of pre-elafin resides in the COOH-terminal region that can be released as mature elafin. The NH(2)-terminal moiety of pre-elafin is characterized by the presence of a specific repeating seq...

BACKGROUND The single-breath N(2) test (sbN(2)-test) is closely related to small airways pathology in resected lung specimens of smokers. We investigated whether uneven ventilation and airway closure are associated with specific markers of airway inflammation as obtained by bronchial biopsies, BAL, and induced sputum in patients with manifest COPD. METHODS Fifty-one patients with stable COPD ...

BACKGROUND Earlier studies have shown that the absolute number of neutrophil granulocytes (NGs) may increase during attack of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE). Whether NGs undergo activation during attack has not yet been investigated. However, as neutrophil elastase (NE) can cleave and inactivate C1-INH which may contribute to the dysregulation of the kallikrei...

Inflammatory responses have been known to contribute to the development of neuronal damage after brain ischemia in experimental animals. Also, neutrophil elastase activity in the plasma has been elevated in the patients with acute cerebral infarction. In order to clarify whether neutrophil elastase distributes into the brain parenchyma and exacerbates neuronal damage following ischemia, we exam...

To define the role of neutrophil elastase (NE) in the progression of acute lung injury (ALI), we examined the effects of post-treatment with a specific NE inhibitor, sivelestat sodium hydrate (sivelestat), on ALI induced by endotoxin (ET) inhalation in hamsters. Inhalation of ET (300 microg/ml, 30 min) in conscious hamsters increased inflammatory cell count, protein concentration, and hemorrhag...

Introduction Genetics of Elastase In vitro Substrates of Elastase—Clues to in vivo Function? Regulation and Function of Elastase Inhibition by and Evasion of Antiproteases Elastase Release by Neutrophils Involvement of Elastase in Neutrophil Transvascular Emigration into the Interstitium Membrane-bound Elastase: Vectorial Migration of the Neutrophil? Cytotoxicity and Wound Healing Evidence for ...