Dexamethasone reduces rat tracheal goblet cell hyperplasia produced by human neutrophil products.
An experimental model leading to goblet cell hyperplasia was developed in order to examine the possible preventive effects of glucocorticosteroids. Human peripheral blood neutrophils were isolated and either freeze-thaw lysed or activated with serum opsonized zymosan. Supernatants from these neutrophil preparations were then instilled transorally into the tracheas of male Sprague-Dawley rats. After 7-35 days, the rats were sacrificed; the lower tracheas were excised, fixed in formalin, and stained with periodic acid-Schiff and alcian blue; and the goblet cells and total epithelial cells were counted. Supernatants from both lysed neutrophils and zymosan-activated neutrophils stimulated a 50% and 42% (respectively) increase in goblet cells after 3 weeks as compared to controls. Purified human neutrophil or porcine pancreatic elastase also caused goblet cell hyperplasia, while sham challenge, challenge with buffer, or challenge with lysates of human mononuclear cells failed to affect goblet cell number. The increase in goblet-cell number was maximal by three weeks and persisted through 35 days. Treatment of animals with glucocorticosteroids administered by the addition of dexamethasone to the drinking water (2 mg/l for 1 week followed by 0.2 mg/l for 2 weeks) ablated the goblet cell hyperplasia produced by neutrophil lysates or elastase alone. We conclude that goblet cell hyperplasia may be induced with insufflated neutrophil products and that this action can be inhibited by treatment with corticosteroids.
Lundgren
J D
JD
Critical Care Medicine Department, Clinical Center, Bethesda, MD 20892.
Kaliner
M
M
Logun
C
C
Shelhamer
J H
JH
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008679:Metaplasia; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000473:pathology*
D003907:Dexamethasone; D010196:Pancreatic Elastase