Many cell types in the airway express the adhesive
glycoprotein for leukocytes
intercellular adhesion molecule-1 (ICAM-1) constitutively and/or in response to inflammatory stimuli. In this study, we identified functions of
ICAM-1 on airway epithelial cells in defense against
infection with Haemophilus influenzae. Initial experiments using a mouse model of airway
infection in which the bacterial inoculum was mixed with
agar beads that localize
inflammation in airways demonstrated that
ICAM-1 expression was required for efficient clearance of H. influenzae. Airway epithelial cell
ICAM-1 expression required few or no leukocytes, suggesting that epithelial cells could be activated directly by interaction with bacteria. Specific inhibition of
ICAM-1 function on epithelial cells by orotracheal injection of
blocking antibodies resulted in decreased leukocyte recruitment and H. influenzae clearance in the airway. Inhibition of endothelial cell
ICAM-1 resulted in a similar decrease in leukocyte recruitment but did not affect bacterial clearance, indicating that epithelial cell
ICAM-1 had an additional contribution to airway defense independent of effects on leukocyte migration. To assess this possibility, we used an in vitro model of neutrophil phagocytosis of bacteria and observed significantly greater engulfment of bacteria by neutrophils adherent to epithelial cells expressing
ICAM-1 compared with nonadherent neutrophils. Furthermore, bacterial phagocytosis and killing by neutrophils after interaction with epithelial cells were decreased when a blocking antibody inhibited
ICAM-1 function. The results indicate that epithelial cell
ICAM-1 participates in neutrophil recruitment into the airway, but its most important role in clearance of H. influenzae may be assistance with neutrophil-dependent bacterial killing.