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

Uller, Lena LU ; Persson, Carl LU ; Källström, Leif and Erjefält, Jonas LU (2001) In American Journal of Respiratory and Critical Care Medicine 164(10). p.1948-1956
Abstract
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,... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
steroids, apoptosis, eosinophils, transmission electron microscopy
in
American Journal of Respiratory and Critical Care Medicine
volume
164
issue
10
pages
1948 - 1956
publisher
Am Thoracic Soc
external identifiers
  • pmid:11734451
  • wos:000172758700037
  • scopus:0035891587
ISSN
1535-4970
DOI
10.1164/rccm2011135
language
English
LU publication?
yes
id
4e6ae331-a1f8-44eb-b63d-d8d214f86e2a (old id 1120343)
date added to LUP
2008-07-17 08:29:02
date last changed
2018-01-07 05:12:27
@article{4e6ae331-a1f8-44eb-b63d-d8d214f86e2a,
  abstract     = {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.},
  author       = {Uller, Lena and Persson, Carl and Källström, Leif and Erjefält, Jonas},
  issn         = {1535-4970},
  keyword      = {steroids,apoptosis,eosinophils,transmission electron microscopy},
  language     = {eng},
  number       = {10},
  pages        = {1948--1956},
  publisher    = {Am Thoracic Soc},
  series       = {American Journal of Respiratory and Critical Care Medicine},
  title        = {Lung tissue eosinophils may be cleared through luminal entry rather than apoptosis: effects of steroid treatment},
  url          = {http://dx.doi.org/10.1164/rccm2011135},
  volume       = {164},
  year         = {2001},
}