Non-allergic models of mucous cell metaplasia and mucus hypersecretion in rat nasal and pulmonary airways.
Mucous cell proliferation and hypersecretion of airway mucus are important pathological features of human respiratory disorders such as asthma and chronic bronchitis. In addition to airborne allergens and infectious agents, inhaled chemical irritants such as ozone and cigarette smoke have been demonstrated to induce changes in airway mucus production. Cellular and molecular mechanisms involved in non-allergic, toxicant-induced mucous cell metaplasia (MCM; transformation of airway epithelium, normally devoid of mucous cells, to secretory epithelium containing numerous mucus-secreting cells) are still unclear. We have used two experimental models of toxicant-induced MCM in the airways of rats to study the epithelial and inflammatory factors involved in the pathogenesis of MCM. Mucin-specific gene expression and MCM are induced in the nasal transitional epithelium (NTE), but not in the bronchiolar epithelium of F344 rats acutely exposed to ozone, an important air pollutant of photochemical smog. Inhalation of endotoxin, a lipopolysaccharide-protein molecule of gram-negative bacteria, induces MCM in the bronchiolar epithelium, but not in the NTE, of rats. Both ozone- and endotoxin-induced MCM are dependent on neutrophilic inflammation. Interestingly, each toxicant enhances the MCM induced by the other toxicant. These synergistic effects elicited by coexposure to ozone and endotoxin are also mediated, in part, by neutrophils.
Harkema
Jack R
JR
College of Veterinary Medicine, Laboratory for Experimental and Toxicologic Pathology, Michigan State University, East Lansing, MI 48824, USA.
Wagner
James G
JG
D000818:Animals; D029721:Drosophila Proteins; D004731:Endotoxins / Q000633:toxicity; D004847:Epithelial Cells / Q000473:pathology; D066246:ErbB Receptors / Q000502:physiology; D005088:Exocrine Glands / Q000378:metabolism / Q000473:pathology; D005089:Exocytosis / Q000502:physiology*; D020397:Goblet Cells / Q000378:metabolism*; D006965:Hyperplasia; D007249:Inflammation; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000502:physiology; D008679:Metaplasia; D009077:Mucins / Q000096:biosynthesis / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology; D009928:Organ Specificity; D010126:Ozone / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface / Q000502:physiology; D012636:Secretory Rate; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D004731:Endotoxins; D008562:Membrane Glycoproteins; D009077:Mucins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D010126:Ozone; D066246:ErbB Receptors