| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
* Department of Medicine and
Department of Pathology, Harvard Medical School, Boston, MA 02115;
Division of Rheumatology, Immunology, and Allergy and
Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115; and
¶ Millennium Pharmaceuticals, Cambridge, MA 02139
The Th2 cell-dependent inflammatory response is a central component of asthma, and the ways in which it is regulated is a critical question. The cysteinyl leukotrienes (cys-LTs) are 5-lipoxygenase pathway products implicated in asthma, in particular, by their function as smooth muscle constrictors of airways and microvasculature. To elucidate additional roles for cys-LTs in the pathobiology of pulmonary inflammation, we used an OVA sensitization and challenge protocol with mice lacking leukotriene C4 synthase (LTC4S), the terminal enzyme for cys-LT generation. Ag-induced pulmonary inflammation, characterized by eosinophil infiltration, goblet cell hyperplasia with mucus hypersecretion, and accumulation and activation of intraepithelial mast cells was markedly reduced in LTC4Snull mice. Furthermore, Ag-specific IgE and IgG1 in serum, Th2 cell cytokine mRNA expression in the lung, and airway hyperresponsiveness to methacholine were significantly reduced in LTC4Snull mice compared with wild-type controls. Finally, the number of parabronchial lymph node cells from sensitized LTC4Snull mice and their capacity to generate Th2 cell cytokines ex vivo after restimulation with Ag were also significantly reduced. In contrast, delayed-type cutaneous hypersensitivity, a prototypic Th1 cell-dependent response, was intact in LTC4Snull mice. These findings provide direct evidence of a role for cys-LTs in regulating the initiation and/or amplification of Th2 cell-dependent pulmonary inflammation.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  A. G. Kaditis, M. G. Ioannou, K. Chaidas, E. I. Alexopoulos, M. Apostolidou, T. Apostolidis, G. Koukoulis, and K. Gourgoulianis Cysteinyl Leukotriene Receptors Are Expressed by Tonsillar T Cells of Children With Obstructive Sleep Apnea Chest, August 1, 2008; 134(2): 324 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Paruchuri, Y. Jiang, C. Feng, S. A. Francis, J. Plutzky, and J. A. Boyce Leukotriene E4 Activates Peroxisome Proliferator-activated Receptor {gamma} and Induces Prostaglandin D2 Generation by Human Mast Cells J. Biol. Chem., June 13, 2008; 283(24): 16477 - 16487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Woszczek, L.-Y. Chen, S. Nagineni, and J. H. Shelhamer IL-10 Inhibits Cysteinyl Leukotriene-Induced Activation of Human Monocytes and Monocyte-Derived Dendritic Cells J. Immunol., June 1, 2008; 180(11): 7597 - 7603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hallgren, T. G. Jones, J. P. Abonia, W. Xing, A. Humbles, K. F. Austen, and M. F. Gurish Pulmonary CXCR2 regulates VCAM-1 and antigen-induced recruitment of mast cell progenitors PNAS, December 18, 2007; 104(51): 20478 - 20483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Jiang, L. A. Borrelli, Y. Kanaoka, B. J. Bacskai, and J. A. Boyce CysLT2 receptors interact with CysLT1 receptors and down-modulate cysteinyl leukotriene dependent mitogenic responses of mast cells Blood, November 1, 2007; 110(9): 3263 - 3270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-R. Blanchet, S. Maltby, D. J. Haddon, H. Merkens, L. Zbytnuik, and K. M. McNagny CD34 facilitates the development of allergic asthma Blood, September 15, 2007; 110(6): 2005 - 2012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Maskrey, A. Bermudez-Fajardo, A. H. Morgan, E. Stewart-Jones, V. Dioszeghy, G. W. Taylor, P. R. S. Baker, B. Coles, M. J. Coffey, H. Kuhn, et al. Activated Platelets and Monocytes Generate Four Hydroxyphosphatidylethanolamines via Lipoxygenase J. Biol. Chem., July 13, 2007; 282(28): 20151 - 20163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ohtsuki, Y. Taketomi, S. Arata, S. Masuda, Y. Ishikawa, T. Ishii, Y. Takanezawa, J. Aoki, H. Arai, K. Yamamoto, et al. Transgenic Expression of Group V, but Not Group X, Secreted Phospholipase A2 in Mice Leads to Neonatal Lethality because of Lung Dysfunction J. Biol. Chem., November 24, 2006; 281(47): 36420 - 36433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Jiang, Y. Kanaoka, C. Feng, K. Nocka, S. Rao, and J. A. Boyce Cutting edge: interleukin 4-dependent mast cell proliferation requires autocrine/intracrine cysteinyl leukotriene-induced signaling. J. Immunol., September 1, 2006; 177(5): 2755 - 2759. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
