Neutrophil-dependent and neutrophil-independent alterations in the nasal epithelium of ozone-exposed rats

Ozone induces epithelial hyperplasia and mucous cell metaplasia (MCM) in na sal transitional epithelium (NTE) of rats. A transient neutrophil influx ac companies upregulation of mucin messenger RNA (mRNA) before the onset of MC M. The present study was designed to examine the role of neutrophils in ozo ne-induced epithelial changes in the NTE of rats. Fourteen hours before inh alation exposure, male F344/N rats were injected intraperitoneally with ant irat neutrophil antiserum to deplete circulating neutrophils, or were injec ted 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 NT E were analyzed to determine the epithelial labeling index; numeric densiti es of neutrophils, total epithelial cells, and mucous secretory cells; amou nt of stored intraepithelial mucosubstances; and steady-state ratMUC-5AC (m ucin) mRNA levels. At 2 h after 3 d of exposure, rats treated with antiseru m had 90% fewer circulating neutrophils than did rats treated with control serum. Antiserum-treated, ozone-exposed rats had 87% fewer infiltrating neu trophils 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 i ntraepithelial mucosubstances and 58% fewer mucous cells in their NTE than did control serum-treated, ozone-exposed rats. Antiserum treatment had no e ffects on ozone-induced epithelial cell proliferation or mucin mRNA upregul ation. The results of this study indicated that ozone-induced MCM was neutr ophil-dependent, whereas ozone-induced epithelial cell proliferation and mu cin gene upregulation were neutrophil-independent.