title: Allergen-induced bone marrow eosinophilopoiesis and airways eosinophilic inflammation in leptin-deficient ob/ob mice.
abstract: Asthma and obesity are growing epidemics in the world. It is well established that obesity worsens the asthma outcomes. High-fat diet-induced obesity in mice exacerbates the pulmonary eosinophilic inflammation. We have used wild-type (WT) and ob/ob mice to further explore the mechanisms by which obesity aggravates the pulmonary eosinophilic inflammation. The eosinophil (EO) number in bronchoalveolar lavage (BAL) fluid, lung tissue, blood, and bone marrow were evaluated at 24, 48, and 72 h after ovalbumin (OVA) challenge in sensitized mice. The basal EO number (phosphate-buffered saline (PBS)-instilled mice) in lung tissue was about 3.5-fold greater in ob/ob compared with WT mice. OVA challenge in ob/ob mice promoted an EO accumulation into the lung that was accompanied by a lower emigration to airways lumen (BAL fluid) in comparison with WT mice. OVA challenge also markedly elevated the number of mature and immature EO in bone marrow of ob/ob mice at 24 h compared with WT group. Blood EO at 48 h was markedly greater in ob/ob mice. Tumor necrosis factor (TNF)-α and interleukin (IL)-10 levels in BAL fluid were significantly higher in ob/ob mice, whereas no changes for IL-5 and eotaxin were found. The IL-6 levels were significantly lower in ob/ob mice. In conclusion, OVA challenge in ob/ob obese mice potentiates eosinophilopoiesis and promotes an accumulation of EO into the lung tissue, delaying their transit to airways lumen. The longer EO remain into the lung tissue is likely to contribute, at least in part, to the asthma worsened by obesity.
authors.affiliation: Department of Pharmacology, University of Campinas, Campinas, Brazil. lintomen@fcm.unicamp.br
authors.forename: Leticia
authors.initials: L
authors.lastname: Lintomen
authors.forename: Marina C
authors.initials: MC
authors.lastname: Calixto
authors.forename: André
authors.initials: A
authors.lastname: Schenka
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005260:Female; D007249:Inflammation; D015850:Interleukin-6 / Q000276:immunology*; D020738:Leptin / Q000172:deficiency* / Q000276:immunology; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000276:immunology* / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000276:immunology* / Q000473:pathology
chemical_list: D000485:Allergens; D016207:Cytokines; D015850:Interleukin-6; D020738:Leptin; D010047:Ovalbumin