IgE mediates broncho-vascular remodeling after neonatal sensitization in mice.
The temporal origins of childhood asthma are incompletely understood. We hypothesize that allergen sensitization which begins in early infancy causes IgE-mediated airway and vascular remodeling, and airway hyper-responsiveness. Mice were sensitized with ovalbumin (OVA) without or with anti-IgE antibody from postnatal day (P) 10 through P42. We studied airway resistance in response to Methacholine (MCh) challenge, bronchoalveolar lavage fluid (BAL) inflammatory cell content, immunohistochemistry for inflammation, alpha-smooth muscle actin (alpha-SMA) and platelet/endothelial cell adhesion molecule (PECAM) proteins, and Western blotting for vascular endothelial growth factor (VEGF) protein. Compared to controls, mice treated with OVA had increased airway resistance (baseline: 192% of control; MCH 12 mg/mL 170% of control; P less than 0.0.5). OVA treatment also increased lung alpha-SMA, VEGF and PECAM compared to controls. Inflammatory cells in the BAL and perivascular and peribronchiolar inflammatory cell infiltrates increased over controls with OVA exposure. These changes were counteracted by anti-IgE treatment. We conclude that mice sensitized in early infancy develop an IgE-mediated hyper-reactive airway disease with airway and vascular remodeling. Preventive approaches in early infancy of at-risk individuals may reduce childhood asthma.
Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, MA.
Anne
A
Chetty
Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, MA.
Gong-Jie
GJ
Cao
Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, MA.
Azeem
A
Sharda
Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, MA.
Theresia
T
Tsay
Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, MA, heber.nielsen@tufts.edu.
Heber C
HC
Nielsen
D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology / Q000473:pathology; D015153:Blotting, Western; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000473:pathology; D007114:Immunization; D007073:Immunoglobulin E / Q000502:physiology*; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D066253:Vascular Remodeling
D007073:Immunoglobulin E