title: Production of leukotriene C4 by peripheral blood leukocytes stimulated with anti-fcepsilonRI antibody, PMA, and fMLP does not correlate with irreversible airway obstruction in asthmatics.
abstract: BACKGROUND
  Airway remodeling has recently emerged as a major problem in an increasing percentage of patients with asthma. Reasons for great diversity in the progression of irreversible bronchoconstriction among asthmatics remain unclear.
  
  
  OBJECTIVE
  The aim of this study was to assess whether the potential ability of leukocytes to produce cysteinyl leukotrienes in response to various stimuli is correlated with magnitude of irreversible airway obstruction in asthmatics.
  
  
  METHODS
  The study sample comprised 76 asthmatics (34 males, mean +/- SD age 52 +/- 13 years), and 35 healthy controls (18 males, 38.2 +/- 15 years). Each subject underwent 2 pulmonary function tests: before and after bronchodilator administration. In addition, approximate annual decline in forced expiratory volume in 1 second (FEV1) (% of predicted) was calculated. Leukotriene C4 (LTC4) production was assessed combining a cellular antigen stimulation test and enzyme-linked immunosorbent assay using Bulhmann Laboratories AG kits. Leukocytes isolated from peripheral blood were stimulated with anti-FcepsilonRI antibody, N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA). In separate tubes each subject's leukocytes were tested for spontaneous LTC4 production. Finally, stimulated LTC4 production was expressed in pg/mL after subtraction of values of spontaneous production.
  
  
  RESULTS
  In asthmatics, baseline FVC% and FEV% values ranged from 24.4% to 122.4% (mean, 75.5%) and from 23.4% to 126.6% (mean, 74.4%), respectively. There were no significant differences between asthmatics and controls in LTC4 production stimulated by anti-FcepsilonRI antibody (P = .79), fMLP (P = .33) or PMA (P = .86). We found no correlation between stimulated LTC4 production and spirometric parameters at baseline or after bronchodilator administration or annual decline in FEV1%.
  
  
  CONCLUSIONS
  Our results do not confirm the hypothesis that airway remodeling in asthma might be related to enhanced ability of leukocytes to produce cysteinyl leukotrienes in response to various stimuli.
authors.affiliation: Department of Internal Medicine and Allergology, Wroclaw Medical University, Wroclaw, Poland. Jerzy.Liebhart@dilnet.wroc.pl
authors.forename: J
authors.initials: J
authors.lastname: Liebhart
authors.forename: W
authors.initials: W
authors.lastname: Medrala
authors.forename: U
authors.initials: U
authors.lastname: Gladysz
authors.forename: W
authors.initials: W
authors.lastname: Barg
authors.forename: E
authors.initials: E
authors.lastname: Liebhart
authors.forename: R
authors.initials: R
authors.lastname: Dobek
authors.forename: A
authors.initials: A
authors.lastname: Dor
authors.forename: A
authors.initials: A
authors.lastname: Kulczak
authors.forename: G
authors.initials: G
authors.lastname: Gogolewski
authors.forename: A
authors.initials: A
authors.lastname: Bigda
authors.forename: B
authors.initials: B
authors.lastname: Panaszek
mesh_terms: D000328:Adult; D000402:Airway Obstruction / Q000276:immunology / Q000503:physiopathology; D000906:Antibodies / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D002478:Cells, Cultured; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D017997:Leukotriene C4 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D017455:Receptors, IgE / Q000276:immunology; D013147:Spirometry; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D017455:Receptors, IgE; D017997:Leukotriene C4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate