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Titolo:
Inhibition of allergic late airway responses by inhaled heparin-derived oligosaccharides
Autore:
Ahmed, T; Ungo, J; Zhou, M; Campo, C;
Indirizzi:
Univ Miami, Sch Med, Mt Sinai Med Ctr, Div Pulm Dis, Miami Beach, FL 33140USA Univ Miami Miami Beach FL USA 33140 iv Pulm Dis, Miami Beach, FL 33140USA
Titolo Testata:
JOURNAL OF APPLIED PHYSIOLOGY
fascicolo: 5, volume: 88, anno: 2000,
pagine: 1721 - 1729
SICI:
8750-7587(200005)88:5<1721:IOALAR>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
LATE ASTHMATIC RESPONSES; MOLECULAR-WEIGHT-DEPENDENCE; MAST-CELL DEGRANULATION; EXERCISE-INDUCED ASTHMA; BRONCHIAL RESPONSIVENESS; BINDING PROTEIN; SULFATE CONTENT; ANTIGEN; HYPERRESPONSIVENESS; ACTIVATION;
Keywords:
heparin oligosaccharides; late-phase reaction;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Ahmed, T Univ Miami, Sch Med, Mt Sinai Med Ctr, Div Pulm Dis, 4300 Alton Rd, Miami Beach, FL 33140 USA Univ Miami 4300 Alton Rd Miami Beach FL USA 33140 h, FL 33140 USA
Citazione:
T. Ahmed et al., "Inhibition of allergic late airway responses by inhaled heparin-derived oligosaccharides", J APP PHYSL, 88(5), 2000, pp. 1721-1729

Abstract

Inhaled heparin has been shown to inhibit allergic bronchoconstriction in sheep that develop only acute responses to antigen (acute responders) but was ineffective in sheep that develop both acute and late airway responses (LAR) (dual responders). Because the antiallergic activity of heparin is molecular-weight dependent, we hypothesized that heparin-derived oligosaccharides (<2,500) with potential anti-inflammatory activity may attenuate the LAR in the dual-responder sheep. Specific lung resistance was measured in 24 dual-responder sheep before and serially for 8 h after challenge with Ascaris suum antigen for demonstration of early airway response (EAR) and LAR, without and after treatment with inhaled medium-, low-, and ultralow-molecular-weight (ULMW) heparins and "non-anticoagulant'' fractions (NAF) of heparin. Airway responsiveness was estimated before and 24 h postantigen as the cumulative provocating dose of carbachol that increased specific lung resistance by 400%. Only ULMW heparins caused a dose-dependent inhibition of antigen-induced EAR and LAR and postantigen airway hyperresponsiveness (AHR), whereas low- and medium-molecular-weight heparins were ineffective. The effects of ULMW heparin and ULMW NAF-heparin were comparable and inhibited theLAR and AHR even when administered "after" the antigen challenge. The ULMWNAF-heparin failed to inhibit the bronchoconstrictor response to histamine, carbachol, and leukotriene D-4, excluding a direct effect on airway smooth muscle. In six sheep, segmental antigen challenge caused a marked increase in bronchoalveolar lavage histamine, which was not prevented by inhaled ULMW NAF-heparin. The results of this study in the dual-responder sheep demonstrate that I) the antiallergic activity of inhaled "fractionated" heparins is molecular-weight dependent, 2) only ULMW heparins inhibit the antigen-induced EAR and LAR and postantigen AKR, and 3) the antiallergic activity is mediated by nonanticoagulant fractions and resides in the ULMW chains of <2,500.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/02/20 alle ore 11:13:19