A role for Leukotriene B4 in the induction of airway hyper-responsiveness was explored through the use of transgenic mice deficient in the BLT1 receptor for LTB4 . Ovalbumin challenge of sensitized wild-type mice resulted in the usual features of experimental asthma, including goblet cell hyperplasia, hyper-responsiveness to inhaled methacholine and elevated BAL fluid concentrations of the Th2 cytokine IL-13. In contrast, BLT1 –/– mice (i.e. genetically modified mice lacking the gene coding for the BLT1 receptor) exhibited significantly lower responses. BLT1 –/– mice also exhibited lower numbers of IL-13-positive T lymphocytes of both the helper (CD4 T Cells) and cytotoxic/suppressor (CD8 + ) types. (more…)

Vascular Endothelial Growth Factor (VEGF), originally described as a vascular permeability factor generating tissue oedema, has been found to exert a range of angiogenic actions, including epithelial cell proliferation, blood vessel formation and endothelial cell survival. Elevated levels of Vascular Endothelial Growth Factor have been detected in bronchial tissues and secretions of asthmatic bronchial individuals, raising questions regarding its possible pathogenetic role in asthma. Using transgenic mice in which local over expression of VEGF could be induced in the lungs by administration of a tetracycline antibiotic demonstrated induction of an asthma-like phenotype with airway inflammation and oedema, hyper-responsiveness and remodelling (airway, parenchymal and vascular). Antigen-induced airway inflammation was accompanied by VEGF production by epithelial cells and TH2 cells, with production by Th1 cells markedly lower. (more…)