Inhibition of eosinophilic inflammation in allergen-challenged TNF receptor p55/p75- and TNF receptor p55-deficient mice

To determine the relative in vivo importance of tumor necrosis factor (TNF) release after allergen challenge to the subsequent endothelial adhesion and recruitment of eosinophils, we have compared eosinophil recruitment in TNF receptor p55/p75-deficient, TNF receptor p55-deficient, and control wild-type mice challenged with allergen. Bronchoalveolar lavage eosinophil recruitment in TNF receptor p55/p75-deficient and TNF receptor p55-deficient mice challenged with ovalbumin was significantly reduced compared with wild-type mice. To determine the mechanism of inhibition of eosinophil recruitment in TNF receptor-deficient mice, we used intravital microscopy to visualize the rolling and firm adhesion of fluorescently labeled mouse eosinophils in the microvasculature of the allergen-challenged mouse mesentery. Eosinophil rolling as well as eosinophil firm adhesion to endothelium were significantly inhibited in allergen-challenged TNF receptor p55/p75-deficient and TNF receptor p55-deficient mice compared with wild-type mice. Overall, these studies demonstrate that TNF, released after allergen challenge, is important in the induction of endothelial cell adhesiveness, a prerequisite for recruitment of circulating eosinophils.