Linked Life Data

9870919

Source:http://linkedlifedata.com/resource/pubmed/id/9870919

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-2-4
pubmed:abstractText
Human monocyte/neutrophil elastase inhibitor (M/NEI) is a fast-acting stoichiometric inhibitor of neutrophil elastase (NE), cathepsin-G, and proteinase-3. Recombinant M/NEI (rM/NEI) was evaluated with a rat model of NE-induced lung damage. rM/NEI was found to protect against pulmonary injury caused by instilled human NE or by a preparation from airway secretions (sputum) of cystic fibrosis patients (CF sol). Human NE instilled into rat lungs produced dose-dependent hemorrhage and increased epithelial permeability, whereas NE incubated in vitro with rM/NEI did neither. Similarly, hemorrhage was induced by CF sol, but not by CF sol incubated in vitro with rM/NEI. To examine its distribution and survival time in airways, rM/NEI was labeled with the fluorochrome Texas Red (rM/NEI-TR) and instilled into rat lungs. Confocal microscopy showed that rM/NEI-TR could be detected on large airways (300 microm) at 5 min, 1 h, 4 h, and 24 h after instillation. Pretreating rats with rM/NEI was found to provide extended protection upon subsequent NE challenge, reducing hemorrhage by 98, 96, and 73%, respectively, at 1, 4, and 24 h after rM/NEI pretreatment. Pretreating rats with rM/NEI similarly conferred protection against subsequent exposure to CF sol, reducing hemorrhage by 95, 86, and 87%, respectively, at 1, 4, and 24 h after pretreatment. The findings that rM/NEI (1) mitigates protease-induced lung injury and (2) remains present and active in the lungs for 24 h after instillation strongly support its potential for treating patients with neutrophil protease-induced inflammatory lung damage, such as occurs in CF and other diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
69-78
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Recombinant human Monocyte/Neutrophil elastase inhibitor protects rat lungs against injury from cystic fibrosis airway secretions.
pubmed:affiliation
Physiology Program, Harvard School of Public Health, Harvard Medical School, Boston, Massachusetts, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't