MULTIPLE ROLES OF LEU-8/MEL-14 IN LEUKOCYTE ADHESION AND FUNCTION

Leu-8 and its murine homologue MEL-14 are members of a new family of adhesion molecules encoded on chromosome-1 that share common structural features, including lectin-like domains and tandem repeats homologous to complement binding proteins. The expression of Leu-8 is rapidly down-regulated during cell activation, both at the transcriptional level, and by a rapid post-translational event at the cell membrane, probably involving direct cleavage of the molecule from the cell surface. Lymphocytes that express Leu-8/MEL-14 bind selectively to HEVs in peripheral lymph nodes, and MEL-14 on neutrophils is thought to be important in the initial localization of neutrophils to sites of inflammation. In addition to its role in leukocyte adhesion, there is evidence that the Leu-8 molecule plays a role in cell function. Anti-Leu-8 monoclonal antibody increases suppressor activity of CD4+, Leu-8+ T cells for immunoglobulin synthesis, and anti-Leu-8 directly inhibits differentiation of Leu-8+ B cells. Together these findings indicate that the Leu-8 molecule in common with other cellular adhesion molecules is important not only in cellular adhesion, but also in modification of cell function.