Linked Life Data

11719302

Source:http://linkedlifedata.com/resource/pubmed/id/11719302

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-11-23
pubmed:abstractText
Many mediators activate eosinophils via transduction pathways involving the enzyme phosphatidylinositol 3-kinase. The initial investigation of wortmannin, a specific inhibitor of PI3-kinase, was of its effect on human and guinea pig eosinophil superoxide (O(2)(-)) release and degranulation in vitro. Subsequently, the effect on allergen- and Sephadex-induced bronchial inflammation and airway hyperresponsiveness (AHR) in vivo in guinea pigs was investigated. Wortmannin potently inhibited complement C5a-induced O(2)(-) generation and eosinophil peroxidase (EPO) release from human eosinophils, with 50% inhibition produced by a 1-10 nM concentration. Both aerosol allergen challenge of sensitized guinea pigs and intravenous injection of Sephadex beads in normal guinea pigs caused, in 24 h, significant eosinophilia and increased EPO activity in bronchoalveolar lavage fluid (BALF) and AHR to intravenous acetylcholine and histamine. In the allergic model, intranasal pretreatment with wortmannin had no effect on BALF eosinophilia, but dose dependently inhibited BALF EPO activity. At 1 mg/kg, the drug abolished the AHR to histamine, but not acetylcholine. In the Sephadex model, the drug significantly inhibited all three parameters (eosinophilia, increased EPO activity, and AHR to both spasmogens). These results show that wortmannin is a potent inhibitor of human eosinophil degranulation and that when administered intranasally can prevent AHR in allergen-challenged guinea pigs, probably by inhibiting eosinophil degranulation, but not their accumulation in BALF. This may be relevant to the possible clinical utility of wortmannin in conditions involving eosinophilic inflammation and AHR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1073-449X
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
164
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1633-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Effect of wortmannin on human eosinophil responses in vitro and on bronchial inflammation and airway hyperresponsiveness in Guinea pigs in vivo.
pubmed:affiliation
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Safat, Kuwait. ezeamuzie@hsc.kuniv.edu.kw
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Evaluation Studies