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Am. J. Respir. Cell Mol. Biol., Volume 18, Number 2, February, 1998 218-225

Inhibition of Pulmonary Eosinophilia in P-Selectin- and ICAM-1-deficient Mice

David H. Broide, Sue Sullivan, Tim Gifford, and P. Sriramarao

Department of Medicine, University of California at San Diego, San Diego, California; and Laboratory of Immunology and Vascular Biology, La Jolla Institute for Experimental Medicine, La Jolla, California

Adhesion molecule expression by pulmonary endothelial cells is considered to play an important role in the recruitment of circulating leukocytes to sites of inflammation in the lung. We have used P-selectin- and intercellular adhesion molecule type 1 (ICAM-1)-deficient mice to determine whether these adhesion molecules are important to pulmonary eosinophil recruitment after allergen challenge. There was a significant inhibition of lung tissue eosinophil recruitment in ICAM-1-deficient mice (~ 84% inhibition compared to wild-type mice) and P-selectin-deficient mice (~ 67% inhibition compared to wild-type mice) 3 h after allergen challenge. The number of bronchoalveolar lavage (BAL) eosinophils in P-selectin-deficient and ICAM-1-deficient mice was also significantly reduced compared with wild-type mice. Levels of BAL eosinophil peroxidase (EPO) were significantly lower in ICAM-1-deficient mice (0.21 ± 0.03 EPO units) compared with wild-type mice (3.34 ± 0.65 EPO units). There was no significant difference in the degree of inhibition of eosinophil recruitment in ICAM-1-deficient mice at the three time points (3, 12, and 24 h) of study after allergen challenge. However, in P-selectin-deficient mice there was a decline in the degree of inhibition of eosinophil recruitment from 3 h (67% inhibition) and 12 h (72% inhibition) postchallenge, to 24 h postchallenge (38% inhibition), suggesting that other adhesion molecules may be playing a more prominent role than P-selectin at later time points. These studies suggest an important role for ICAM-1 and P-selectin in eosinophil recruitment to the lung after allergen challenge.




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