Am. J. Respir. Crit. Care Med., Volume 164, Number 8, October 2001, 1495-1500

Inhaled Leukotriene E₄, But Not Leukotriene D₄, Increased Airway Inflammatory Cells in Subjects with Atopic Asthma

GAIL M. GAUVREAU, KRISHNAN N. PARAMESWARAN, RICHARD M. WATSON, and PAUL M. O'BYRNE

Asthma Research Group, St. Joseph's Healthcare and the Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Allergen-induced late airway responses are associated with increased numbers of airway eosinophils and basophils. The purpose of this study was to compare and contrast the effects of inhaled cysteinyl leukotrienes LTD₄ and LTE₄, which are released during allergen- induced airway responses, and allergen, on airway inflammatory cells. Fifteen subjects with atopic, mild asthma inhaled diluent, LTD₄, LTE₄, and allergen. Spirometry was performed for 7 h, and sputum inflammatory cells were measured before, 7 h, and 24 h after challenges. The maximum early percent fall in FEV₁ was 23.6 ± 1.4%, 21.6 ± 2.3%, 29.3 ± 2.4%, and 4.0 ± 1.1% after LTD₄, LTE₄, allergen, and diluent, respectively. Only inhaled LTE₄ and allergen significantly increased sputum eosinophils at 7 h and 24 h, and sputum basophils at 7 h. Six additional subjects underwent airway biopsies 4 h after inhalation. There were significantly more eosinophils in the lamina propria after inhalation of LTE₄ compared with LTD₄ and diluent (p < 0.05). These results suggest cysteinyl leukotrienes play a role in eosinophil migration into the airways in allergic asthma, and for the same degree of bronchoconstriction, inhaled LTE₄ causes more tissue and airway eosinophilia than LTD₄.

This article has been cited by other articles:

				S. Paruchuri, H. Tashimo, C. Feng, A. Maekawa, W. Xing, Y. Jiang, Y. Kanaoka, P. Conley, and J. A. Boyce Leukotriene E4-induced pulmonary inflammation is mediated by the P2Y12 receptor J. Exp. Med., October 26, 2009; 206(11): 2543 - 2555. [Abstract] [Full Text] [PDF]

				A. Maekawa, Y. Kanaoka, W. Xing, and K. F. Austen Functional recognition of a distinct receptor preferential for leukotriene E4 in mice lacking the cysteinyl leukotriene 1 and 2 receptors PNAS, October 28, 2008; 105(43): 16695 - 16700. [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]

				K. Parameswaran, R. Watson, G. M. Gauvreau, R. Sehmi, and P. M. O'Byrne The Effect of Pranlukast on Allergen-induced Bone Marrow Eosinophilopoiesis in Subjects with Asthma Am. J. Respir. Crit. Care Med., April 15, 2004; 169(8): 915 - 920. [Abstract] [Full Text] [PDF]

				I. Machida, H. Matsuse, Y. Kondo, T. Kawano, S. Saeki, S. Tomari, Y. Obase, C. Fukushima, and S. Kohno Cysteinyl Leukotrienes Regulate Dendritic Cell Functions in a Murine Model of Asthma J. Immunol., February 1, 2004; 172(3): 1833 - 1838. [Abstract] [Full Text] [PDF]

				K. Chibana, Y. Ishii, T. Asakura, and T. Fukuda Up-Regulation of Cysteinyl Leukotriene 1 Receptor by IL-13 Enables Human Lung Fibroblasts to Respond to Leukotriene C4 and Produce Eotaxin J. Immunol., April 15, 2003; 170(8): 4290 - 4295. [Abstract] [Full Text] [PDF]

				S. O'Sullivan, M. Akveld, C. M. Burke, and L. W. Poulter Effect of the Addition of Montelukast to Inhaled Fluticasone Propionate on Airway Inflammation Am. J. Respir. Crit. Care Med., March 1, 2003; 167(5): 745 - 750. [Abstract] [Full Text] [PDF]

				A. Oommen and J. Grigg Urinary leukotriene E4 in preschool children with acute clinical viral wheeze Eur. Respir. J., January 1, 2003; 21(1): 149 - 154. [Abstract] [Full Text] [PDF]

				Z. Csoma, S. A. Kharitonov, B. Balint, A. Bush, N. M. Wilson, and P. J. Barnes Increased Leukotrienes in Exhaled Breath Condensate in Childhood Asthma Am. J. Respir. Crit. Care Med., November 15, 2002; 166(10): 1345 - 1349. [Abstract] [Full Text] [PDF]

				R. Leigh, D. Vethanayagam, M. Yoshida, R. M. Watson, T. Rerecich, M. D. Inman, and P. M. O'Byrne Effects of Montelukast and Budesonide on Airway Responses and Airway Inflammation in Asthma Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1212 - 1217. [Abstract] [Full Text] [PDF]

				K. Parameswaran, G. Cox, K. Radford, L. J. Janssen, R. Sehmi, and P. M. O'Byrne Cysteinyl Leukotrienes Promote Human Airway Smooth Muscle Migration Am. J. Respir. Crit. Care Med., September 1, 2002; 166(5): 738 - 742. [Abstract] [Full Text] [PDF]

				M. J. TOBIN Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2001 Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 598 - 618. [Full Text] [PDF]