Contraction of human bronchial smooth muscle caused by activated human eosinophils.
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)
Rabe
K F
KF
Krankenhaus Grosshansdorf, Zentrum für Pneumologie und Thoraxchirurgie, LVA Hamburg, Germany.
Muñoz
N M
NM
Vita
A J
AJ
Morton
B E
BE
Magnussen
H
H
Leff
A R
AR
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
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