title: Restoration of the normal Clara cell phenotype after chronic allergic inflammation.
abstract: Bronchiolar Clara cells play a critical role in lung homoeostasis. The main goal of this study was to evaluate the effects of chronic allergy on these cells and the efficacy of budesonide (BUD) and montelukast (MK) in restoring their typical phenotypes after ovalbumin-induced chronic allergy in mice. Chronic allergy induced extensive bronchiolar Alcian blue-periodic acid-Schiff (AB/PAS)-positive metaplasia. In addition, cells accumulated numerous big electron-lucent granules negative for Clara cell main secretory protein (CC16), and consequently, CC16 was significantly reduced in bronchoalveolar lavage. A concomitant reduction in SP-D and CYP2E1 content was observed. The phenotypic changes induced by allergy were pharmacologically reversed by both treatments; MK was more efficient than BUD in doing so. MK decreased AB/PAS reactivity to control levels whereas they remained persistently elevated after BUD. Moreover, most non-ciliated cells recovered their normal morphology after MK, whereas for BUD normal cells coexisted with 'transitional' cells that contained remnant mucous granules and stained strongly for CC16 and SP-D. Glucocorticoids were also less able to reduce inflammatory infiltration and maintained higher percentage of neutrophils, which may have contributed to prolonged mucin expression. These results show that chronic allergy-induced mucous metaplasia of Clara cells affects their defensive mechanisms. However, anti-inflammatory treatments were able to re-establish the normal phenotype of Clara cell, with MK being more efficient at restoring a normal profile than BUD. This study highlights the role of epithelial cells in lung injuries and their contribution to anti-inflammatory therapies.
authors.affiliation: Centro de Microscopía Electrónica, INICSA-CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Felix D
authors.initials: FD
authors.lastname: Roth
authors.forename: Amado A
authors.initials: AA
authors.lastname: Quintar
authors.forename: Carolina
authors.initials: C
authors.lastname: Leimgruber
authors.forename: Luciana
authors.initials: L
authors.lastname: García
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Uribe Echevarría
authors.forename: Alicia I
authors.initials: AI
authors.lastname: Torres
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Maldonado
mesh_terms: D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D019819:Budesonide / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D003521:Cyclopropanes; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004195:Disease Models, Animal; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects; D010641:Phenotype; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D013440:Sulfides; D014598:Uteroglobin / Q000378:metabolism
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D003521:Cyclopropanes; D037663:Pulmonary Surfactant-Associated Protein D; D011804:Quinolines; C556390:Scgb1a1 protein, mouse; D013440:Sulfides; D019819:Budesonide; D010047:Ovalbumin; D014598:Uteroglobin; D019392:Cytochrome P-450 CYP2E1; C093875:montelukast
keywords: CC16; Clara cells; asthma treatment; chronic inflammation