Inhibition of Eosinophil Rolling and Recruitment in P-Selectin– and Intracellular Adhesion Molecule-1–Deficient Mice

Abstract

To determine the relative in vivo importance of endothelial expressed adhesion molecules to eosinophil rolling, adhesion, and transmigration, we have induced eosinophilic peritonitis using ragweed allergen in P-selectin–deficient, intracellular adhesion molecule-1 (ICAM-1)–deficient and control wild-type mice. Circulating leukocytes visualized by intravital microscopy exhibited reduced rolling and firm adhesion in P-selectin–deficient mice and reduced firm adhesion in ICAM-1–deficient mice. Eosinophils exhibited reduced rolling and firm adhesion to endothelium in P-selectin–deficient mice. Eosinophil recruitment in P-selectin–deficient mice (∼75% inhibition of eosinophil recruitment) and ICAM-1–deficient mice (∼67% inhibition of eosinophil recruitment) was significantly reduced compared with wild-type mice. Eosinophil recruitment was not completely inhibited in P-selectin/ICAM-1 double-mutant mice (eosinophil recruitment inhibited ∼62%). However, pretreatment of P-selectin/ICAM-1–deficient mice with an anti-vascular cell adhesion molecule (VCAM) antibody induced near complete inhibition of eosinophil recruitment. Overall, these studies show that eosinophil rolling and firm adhesion is significantly reduced in P-selectin–deficient mice and that P-selectin, ICAM-1, and VCAM are important to eosinophil peritoneal recruitment after ragweed challenge.