Neutrophil-dependent and neutrophil-independent alterations in the nasal epithelium of ozone-exposed rats.
Ozone induces epithelial hyperplasia and mucous cell metaplasia (MCM) in nasal transitional epithelium (NTE) of rats. A transient neutrophil influx accompanies upregulation of mucin messenger RNA (mRNA) before the onset of MCM. The present study was designed to examine the role of neutrophils in ozone-induced epithelial changes in the NTE of rats. Fourteen hours before inhalation exposure, male F344/N rats were injected intraperitoneally with antirat neutrophil antiserum to deplete circulating neutrophils, or were injected with normal (control) serum. Rats were then exposed to 0 ppm (filtered air) or 0.5 ppm ozone (8 h/d) for 1 or 3 d. Maxilloturbinates lined with NTE were analyzed to determine the epithelial labeling index; numeric densities of neutrophils, total epithelial cells, and mucous secretory cells; amount of stored intraepithelial mucosubstances; and steady-state ratMUC-5AC (mucin) mRNA levels. At 2 h after 3 d of exposure, rats treated with antiserum had 90% fewer circulating neutrophils than did rats treated with control serum. Antiserum-treated, ozone-exposed rats had 87% fewer infiltrating neutrophils than did control serum-treated, ozone-exposed rats. At 4 d after 3 d of exposure, antiserum-treated, ozone-exposed rats had 66% less stored intraepithelial mucosubstances and 58% fewer mucous cells in their NTE than did control serum-treated, ozone-exposed rats. Antiserum treatment had no effects on ozone-induced epithelial cell proliferation or mucin mRNA upregulation. The results of this study indicated that ozone-induced MCM was neutrophil-dependent, whereas ozone-induced epithelial cell proliferation and mucin gene upregulation were neutrophil-independent.
Departments of Pathology and Pharmacology, and Toxicology, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
H Y
HY
Cho
J A
JA
Hotchkiss
C B
CB
Bennett
J R
JR
Harkema
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004847:Epithelial Cells / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008679:Metaplasia; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D010126:Ozone / Q000633:toxicity*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation
D009077:Mucins; D012333:RNA, Messenger; D010126:Ozone; D004247:DNA