Lung tissue eosinophils may be cleared through luminal entry rather than apoptosis: effects of steroid treatment.

Spontaneous or steroid-induced eosinophil apoptosis occurring in vitro has not been demonstrated in lung tissues in vivo. This study examines cell apoptosis in rat lungs using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) technique and transmission electron microscopy (TEM). After establishing sustained lung edema and eosinophilia by challenge with Sephadex beads intratracheally, budesonide treatment was started intratracheally. Sephadex alone increased the total number of apoptotic cells, which were not efficiently engulfed by macrophages or other cells, in vivo. Yet apoptotic tissue eosinophils were exceedingly rare (1 of 360 TEM-analyzed eosinophils). By contrast, approximately 20% of eosinophils in the airway lumen were apoptotic, and unengulfed. Budesonide promptly inhibited edema but 3 d of steroid treatment were required to reduce the established tissue eosinophilia. Not at any time point did budesonide induce eosinophil apoptosis (0 of 318 TEM-analyzed tissue eosinophils). We conclude that (1) eosinophil apoptosis can occur but is a rare event in vivo in respiratory tract tissues; (2) airway tissue eosinophils, rather than undergoing apoptosis, are eliminated by migration into airway lumen followed by apoptosis and mucociliary clearance; (3) anti-inflammatory steroid treatment may not increase eosinophil apoptosis in vivo nor may it affect the luminal entry of eosinophils; (4) steroids permit elimination of eosinophils into airway lumen and slowly resolve established lung eosinophilia.
AuthorsL Uller, C G Persson, L Källström, J S Erjefält
JournalAmerican journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 164 Issue 10 Pt 1 Pg. 1948-56 (Nov 15 2001) ISSN: 1073-449X [Print] United States
PMID11734451 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents
  • Tumor Necrosis Factor-alpha
  • Budesonide
  • sephadex
  • Dextrans
  • Animals
  • Anti-Inflammatory Agents (pharmacology, therapeutic use)
  • Apoptosis (physiology)
  • Bronchoalveolar Lavage Fluid (cytology, immunology)
  • Budesonide (pharmacology, therapeutic use)
  • Dextrans
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • In Situ Nick-End Labeling
  • Inflammation
  • Leukocyte Count
  • Male
  • Microscopy, Electron, Scanning Transmission
  • Mucociliary Clearance (drug effects, physiology)
  • Pulmonary Edema (chemically induced, drug therapy, immunology, pathology)
  • Pulmonary Eosinophilia (chemically induced, drug therapy, immunology, pathology)
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha (analysis)

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