ICAM-1 and CD44 expression in human bronchial epithelium and the role of CD44 isoforms in cell adhesion, migration, and repair\dShih-hsing Leir.

Abstract

Mechanical damage of confluent epithelial cells induced the expression of CD44 on the cells up to 500 &mu;m from the wound edge and for up to 48 hours. Before cell confluence, the expression of CD44 at low cell densities was significantly higher than in confluent cultures, while ICAM-1 was lower. IFNγ and TNFα co-stimulation increased ICAM-1 expression significantly, while little change was seen in CD44. IL-1β and IL-4 induced the expression of CD44s, CD44v3 and CD44v9. Individual primary epithelial cells expressed several CD44 isoforms, while CD44 isoforms were undetectable in columnar epithelial cells from human airway. Down-regulation of v8-v9-v10 isoforms and small decreases of v6-v7-v8-v9-v10 and a v3-containing isoforms were seen in the cells with cytokine treatments and mechanical damage. In addition, the function of CD44 was investigated in cell adhesion and migration. Cytokines induced a CD44s-dependent cell adhesion to hyaluronic acid (HA). IFNγ-induced cell binding to HA without increasing the level of cell surface CD44 indicated that other mechanisms are involved in the modulation of CD44/HA binding. CD44 antibodies inhibited cell migration and demonstrated that CD44 plays an important role in cell migration, and may be associated with the repair processes of bronchial epithelium. I have found increased CD44 protein expression or changes in the alternative splicing of CD44 isoforms during the repair of epithelial damage. This study describes the sub-cellular expression and regulation of ICMA-1 and CD44, and provides some indication of functions of these CAMs in human bronchial epithelial cells.</p