title: Contraction of human bronchial smooth muscle caused by activated human eosinophils.
abstract: We assessed the effect of activated eosinophils isolated from human peripheral blood in causing contraction of explanted human bronchi in vitro. Sixty-three epithelium-intact fifth generation airway sections were obtained from 16 subjects undergoing lung resection for carcinoma. Eosinophils were isolated by negative immunoselection, and activation with 10(-7) M platelet-activating factor (PAF) was confirmed by measurements of eosinophil peroxidase (EPO) secretion and superoxide (O2-.) generation. EPO secretion increased from 68.6 +/- 13.4 ng/10(6) cells to 420 +/- 125 ng/10(6) cells after activation with PAF (P < 0.05). Similarly, PAF-induced O2-. generation increased from 15.3 +/- 4.64 nmol cytochrome c reduced/10(5) cells to 44.2 +/- 8.50 nmol cytochrome c reduced/10(5) cells (P < 0.05). Cells were instilled into an isolated airway pouch preparation, and, 60 min later, airway contractile responses were determined by optical micrometry as percent decrease in lumenal diameter (%decrease) and percent increase in wall thickness (%increase) using a calibrated magnifying lens. Treatment with either vehicle, PAF alone, or untreated eosinophils had no effect on airway caliber or thickness. PAF-activated cells caused a 30.5 +/- 1.52% decrease in airway caliber (P < 0.001 vs. untreated cells) and a 36.6 +/- 2.54% increase in wall thickness (P < 0.001 vs. untreated cells). Preincubation with A63162, a 5-lipoxygenase inhibitor, caused concentration-dependent inhibition of airway narrowing. After 10(-5) M A63162, decrease in airway diameter caused by PAF was 8.00 +/- 0.10% vs. 30.5 +/- 1.52% for PAF alone (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Krankenhaus Grosshansdorf, Zentrum für Pneumologie und Thoraxchirurgie, LVA Hamburg, Germany.
authors.forename: K F
authors.initials: KF
authors.lastname: Rabe
authors.forename: N M
authors.initials: NM
authors.lastname: Muñoz
authors.forename: A J
authors.initials: AJ
authors.lastname: Vita
authors.forename: B E
authors.initials: BE
authors.lastname: Morton
authors.forename: H
authors.initials: H
authors.lastname: Magnussen
authors.forename: A R
authors.initials: AR
authors.lastname: Leff
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D016084:Bronchoconstriction / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010647:Phenyl Ethers; D010972:Platelet Activating Factor / Q000494:pharmacology
chemical_list: D000081:Acetamides; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010647:Phenyl Ethers; D010972:Platelet Activating Factor; C068663:N-hydroxy-N-(1-(4-(phenylmethoxy)phenyl)ethyl)-acetamide