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Titolo:
SCF-induced airway hyperreactivity is dependent on leukotriene production
Autore:
Oliveira, SHP; Hogaboam, CM; Berlin, A; Lukacs, NW;
Indirizzi:
Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 Dept Pathol, Ann Arbor, MI 48109 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
fascicolo: 6, volume: 280, anno: 2001,
pagine: L1242 - L1249
SICI:
1040-0605(200106)280:6<L1242:SAHIDO>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
STEM-CELL FACTOR; C-KIT LIGAND; FC-EPSILON-RI; MAST-CELLS; CYTOKINE PRODUCTION; ALPHA PRODUCTION; MESSENGER-RNA; TNF-ALPHA; IFN-GAMMA; IN-VITRO;
Keywords:
bone marrow-derived mast cells; stem cell factor; bronchoalveolar lavage; 5-lipoxygenase activating protein;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Lukacs, NW Univ Michigan, Sch Med, Dept Pathol, 1301 Catherine, Ann Arbor,MI 48109 USA Univ Michigan 1301 Catherine Ann Arbor MI USA 48109 I 48109 USA
Citazione:
S.H.P. Oliveira et al., "SCF-induced airway hyperreactivity is dependent on leukotriene production", AM J P-LUNG, 280(6), 2001, pp. L1242-L1249

Abstract

Stem cell factor (SCF) is directly involved in the induction of airway hyperreactivity during allergen-induced pulmonary responses in mouse models. In these studies, we examined the specific mediators and mechanisms by whichSCF can directly induce airway hyperreactivity via mast cell activation. Initial in vitro studies with bone marrow-derived mast cells indicated that SCF was able to induce the production of bronchospastic leukotrienes, LTC4 and LTE4. Subsequently, when SCF was instilled in the airways of naive mice, we were able to observe a similar induction of LTC4 and LTE4 in the bronchoalveolar lavage (BAL) fluid and lungs of treated mice. These in vivo studies clearly suggested that the previously observed SCF-induced airway hyperreactivity may be related to the leukotriene production after SCF stimulation. To further investigate whether the released leukotrienes were the mediators of the SCF-induced airway hyperreactivity, an inhibitor of 5-lipoxygenase (5-LO) binding to the 5-LO activating protein (FLAP) was utilized. The FLAP inhibitor MK-886, given to the animals before intratracheal SCF administration, significantly inhibited the release of LTC4 and LTE4 into the BALfluid. More importantly, use of the FLAP inhibitor nearly abrogated the SCF-induced airway hyperreactivity. In addition, blocking the LTD4/E-4, but not LTB4, receptor attenuated the SCF-induced airway hyperreactivity. In addition, the FLAP inhibitor reduced other mast-derived mediators, including histamine and tumor necrosis factor. Altogether, these studies indicate thatSCF-induced airway hyperreactivity is dependent upon leukotriene-mediated pathways.

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Documento generato il 30/03/20 alle ore 13:35:16