| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602
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 which SCF 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 BAL fluid. More importantly, use of the FLAP inhibitor nearly abrogated the SCF-induced airway hyperreactivity. In addition, blocking the LTD4/E4, 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 that SCF-induced airway hyperreactivity is dependent upon leukotriene-mediated pathways.
bone marrow-derived mast cells; stem cell factor; bronchoalveolar lavage; 5-lipoxygenase activating protein
This article has been cited by other articles:
|
|
 |
|
  V. Dolgachev, M. Thomas, A. Berlin, and N. W. Lukacs Stem cell factor-mediated activation pathways promote murine eosinophil CCL6 production and survival J. Leukoc. Biol., April 1, 2007; 81(4): 1111 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Berlin and N. W. Lukacs Treatment of Cockroach Allergen Asthma Model with Imatinib Attenuates Airway Responses Am. J. Respir. Crit. Care Med., January 1, 2005; 171(1): 35 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Schottelius, C. Giesen, K. Asadullah, I. M. Fierro, S. P. Colgan, J. Bauman, W. Guilford, H. D. Perez, and J. F. Parkinson An Aspirin-Triggered Lipoxin A4 Stable Analog Displays a Unique Topical Anti-Inflammatory Profile J. Immunol., December 15, 2002; 169(12): 7063 - 7070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. P. Oliveira, D. D. Taub, J. Nagel, R. Smith, C. M. Hogaboam, A. Berlin, and N. W. Lukacs Stem cell factor induces eosinophil activation and degranulation: mediator release and gene array analysis Blood, December 15, 2002; 100(13): 4291 - 4297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Mellor, K. F. Austen, and J. A. Boyce Cysteinyl Leukotrienes and Uridine Diphosphate Induce Cytokine Generation by Human Mast Cells Through an Interleukin 4-regulated Pathway that Is Inhibited by Leukotriene Receptor Antagonists J. Exp. Med., March 4, 2002; 195(5): 583 - 592. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Page, A. J. Ammit, J. L. Black, and C. L. Armour Human mast cell and airway smooth muscle cell interactions: implications for asthma Am J Physiol Lung Cell Mol Physiol, December 1, 2001; 281(6): L1313 - L1323. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
