title: Expression of leukotriene biosynthetic enzymes in tonsillar tissue of children with obstructive sleep apnea: a prospective nonrandomized study.
abstract: OBJECTIVE
  Cysteinyl leukotrienes (CysLTs) potentially promote adenotonsillar hypertrophy in children with obstructive sleep apnea (OSA). Previous studies have identified CysLTs and their receptors in tonsillar tissue from children with OSA.
  
  
  OBJECTIVE
  To demonstrate expression of the leukotriene biosynthetic enzymes 5-lipoxygenase (5-LO), 5-lipoxygenase activating protein (FLAP), leukotriene A(4) hydrolase (LTA(4)H), and leukotriene C(4) synthase (LTC(4)S) in T and B tonsillar lymphocytes from pediatric patients with OSA. It was hypothesized that children with OSA have greater expression of biosynthetic enzymes for CysLTs (5-LO, FLAP, and LTC(4)S) in their tonsillar tissue than do children with recurrent tonsillitis (RT), who were enrolled as controls.
  
  
  METHODS
  This prospective, nonrandomized study was performed at a tertiary care university hospital on 13 children with OSA and adenotonsillar hypertrophy undergoing adenotonsillectomy and 12 children without OSA also undergoing tonsillectomy for RT. Tonsillar tissue from children with OSA or RT was examined for 5-LO, FLAP, LTA(4)H, and LTC(4)S expression under real time-quantitative polymerase chain reaction (RT-qPCR), flow cytometry (FC), and confocal laser scanning microscopy (CM).
  
  
  METHODS
  Expression of biosynthetic enzymes for CysLTs (5-LO, FLAP, and LTC(4)S) was the main outcome measure. Patients with OSA and control patients with RT were compared for numbers of copies of 5-LO, FLAP, and LTC(4)S messenger RNA (by RT-qPCR) in T or B tonsillar lymphocytes and proportions of CD3(+) or CD19(+) tonsillar lymphocytes that expressed 5-LO, FLAP, and LTC(4)S (by FC).
  
  
  RESULTS
  Messenger RNA for all 4 enzymes was detected in T and B lymphocytes from both study groups, and expression of all biosynthetic enzymes was demonstrated in participants with OSA and RT by FC. Patients with OSA differed from controls in the proportions (median [10th-90th percentile]) of LTC(4)S(+) CD3(+) T lymphocytes (23.31% [8.64%-50.07%] vs 10.81% [3.48%-23.32%], respectively) (P = .01) and LTC(4)S(+) CD19(+) B lymphocytes (20.66% [14.62%-65.77%] vs 12.53% [2.87%-36.64%], respectively) (P = .01) detected by FC. Immunoreactivity for the 4 enzymes was detected by CM in B lymphocytes of mantle zones and T lymphocytes of extrafollicular areas.
  
  
  CONCLUSIONS
  Leukotriene biosynthetic enzymes are expressed in tonsillar lymphocytes, and the previously reported detection of CysLTs in tonsillar tissue from children with OSA may be attributed to endogenous synthesis. Enhanced expression of LTC(4)S is a potential target for pharmacologic interventions in OSA.
authors.affiliation: Pediatric Pulmonology Unit and Sleep Disorders Laboratory, First University Department of Pediatrics, University of Athens School of Medicine, Athens, Greece2Aghia Sophia Children's Hospital, Athens, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Tsaoussoglou
authors.affiliation: Pediatric Pulmonology Unit and Sleep Disorders Laboratory, First University Department of Pediatrics, University of Athens School of Medicine, Athens, Greece2Aghia Sophia Children's Hospital, Athens, Greece.
authors.forename: Souzana
authors.initials: S
authors.lastname: Hatzinikolaou
authors.affiliation: Department of Pathology, University of Athens School of Medicine, Athens, Greece.
authors.forename: George E
authors.initials: GE
authors.lastname: Baltatzis
authors.affiliation: Pediatric Pulmonology Unit and Sleep Disorders Laboratory, First University Department of Pediatrics, University of Athens School of Medicine, Athens, Greece2Aghia Sophia Children's Hospital, Athens, Greece.
authors.forename: Loukia
authors.initials: L
authors.lastname: Lianou
authors.affiliation: Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Maragozidis
authors.affiliation: Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
authors.forename: Nikolaos A A
authors.initials: NA
authors.lastname: Balatsos
authors.affiliation: Pediatric Pulmonology Unit and Sleep Disorders Laboratory, First University Department of Pediatrics, University of Athens School of Medicine, Athens, Greece2Aghia Sophia Children's Hospital, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Chrousos
authors.affiliation: Pediatric Pulmonology Unit and Sleep Disorders Laboratory, First University Department of Pediatrics, University of Athens School of Medicine, Athens, Greece2Aghia Sophia Children's Hospital, Athens, Greece.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Kaditis
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins / Q000378:metabolism; D000233:Adenoidectomy; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001402:B-Lymphocytes / Q000201:enzymology; D002648:Child; D003545:Cysteine / Q000378:metabolism*; D004851:Epoxide Hydrolases / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D014066:Palatine Tonsil / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D017286:Polysomnography; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000201:enzymology*; D011795:Surveys and Questionnaires; D013601:T-Lymphocytes / Q000201:enzymology; D014068:Tonsillectomy
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D001094:Arachidonate 5-Lipoxygenase; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C041116:leukotriene-C4 synthase; D003545:Cysteine; C043134:leukotriene A4 hydrolase