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 ( approximately 75% inhibition of eosinophil recruitment) and ICAM-1-deficient mice ( approximately 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 approximately 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.