Am. J. Respir. Crit. Care Med., Volume 164, Number 11, December 2001, 2051-2056

Leukotriene and Prostanoid Pathway Enzymes in Bronchial Biopsies of Seasonal Allergic Asthmatics

MICHELLE L. SEYMOUR, SABINA RAK, DANIEL ÅBERG, GERT C. RIISE, JOHN F. PENROSE, YOSHIHIDE KANAOKA, K. FRANK AUSTEN, STEPHEN T. HOLGATE, and ANTHONY P. SAMPSON

Division of Respiratory Cell & Molecular Biology, Southampton General Hospital, Southampton, United Kingdom; Allergy Centre, Sahlgrenska University Hospital, Gothenberg, Sweden; and Department of Medicine, Harvard Medical School, Boston, Massachusetts

Cysteinyl-leukotrienes and prostaglandin D₂ generated by the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways, respectively, cause bronchoconstriction, leukocyte recruitment, and bronchial hyperresponsiveness in asthma. We characterized the cellular expression of 5-LO and COX enzymes using immunohistochemistry on bronchial biopsies from 12 allergic asthmatic patients before and during seasonal exposure to birch pollen. Bronchial responsiveness (p = 0.004) and symptoms (p < 0.005) increased and peak expiratory flow (PEF; p  0.02) decreased in the pollen season. In-season biopsies had 2-fold more cells immunostaining for 5-LO (p = 0.02), 5-LO-activating protein (FLAP; p = 0.04), and leukotriene (LT)A₄ hydrolase (p = 0.05), and 4-fold more for the terminal enzyme for cysteinyl-leukotriene synthesis, LTC₄ synthase (p = 0.02). Immunostaining for COX-1, COX-2, and PGD₂ synthase was unchanged. Increased staining for LTC₄ synthase was due to increased eosinophils (p = 0.035) and an increased proportion of eosinophils expressing the enzyme (p = 0.047). Macrophages also increased (p = 0.019), but mast cells and T-lymphocyte subsets were unchanged. Inverse correlations between PEF and 5-LO⁺ cell counts link increased expression of 5-LO pathway enzymes in eosinophils and macrophages within the bronchial mucosa to deterioration of lung function during seasonal allergen exposure.

This article has been cited by other articles:

				T. Kobayashi, Y. Takaku, A. Yokote, H. Miyazawa, T. Soma, K. Hagiwara, M. Kanazawa, and M. Nagata Interferon-{beta} augments eosinophil adhesion-inducing activity of endothelial cells Eur. Respir. J., December 1, 2008; 32(6): 1540 - 1547. [Abstract] [Full Text] [PDF]

				J. M. Owens, K. R. Shroyer, and T. T. Kingdom Expression of cyclooxygenase and lipoxygenase enzymes in nasal polyps of aspirin-sensitive and aspirin-tolerant patients. Arch Otolaryngol Head Neck Surg, June 1, 2006; 132(6): 579 - 587. [Abstract] [Full Text] [PDF]

				I. Kikuchi, S. Kikuchi, T. Kobayashi, K. Hagiwara, Y. Sakamoto, M. Kanazawa, and M. Nagata Eosinophil Trans-Basement Membrane Migration Induced by Interleukin-8 and Neutrophils Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 760 - 765. [Abstract] [Full Text] [PDF]

				L. Wang, P. Chitano, and T. M. Murphy Length oscillation induces force potentiation in infant guinea pig airway smooth muscle Am J Physiol Lung Cell Mol Physiol, December 1, 2005; 289(6): L909 - L915. [Abstract] [Full Text] [PDF]

				Y. Cai, L. Bjermer, and T. S. Halstensen Bronchial Mast Cells Are the Dominating LTC4S-Expressing Cells in Aspirin-Tolerant Asthma Am. J. Respir. Cell Mol. Biol., December 1, 2003; 29(6): 683 - 693. [Abstract] [Full Text] [PDF]

				M. J. Tobin Compliance (COMmunicate PLease wIth Less Abbreviations, Noun Clusters, and Exclusiveness) Am. J. Respir. Crit. Care Med., December 15, 2002; 166(12): 1534 - 1536. [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]