page 945) now provide important new insights into phagocyte fusion, suggesting that the process may differ considerably from other types of cell fusion.
Earlier work identified several cell surface proteins required for phagocyte fusion, but the authors focused on CD9 and CD81, transmembrane proteins in the tetraspanin family that promote the fusion of gametes, myoblasts, and virus-infected cells. Surprisingly, the expression of both proteins is elevated in mononuclear phagocytes cultured under normal conditions, but under fusogenic conditions CD9 and CD81 expression is reduced. Antibodies against either tetraspanin increase phagocyte fusion, and macrophages from mice lacking CD9 or CD81 have enhanced fusion capacity when stimulated.
Based on results from other cell types, CD9 and CD81 had been considered fusion promoters, but they apparently inhibit the process in phagocytes, indicating fundamental regulatory differences between macrophage and nonmacrophage fusion. The authors speculate that alterations in tetraspanin activity may contribute to the progression of diseases that involve multinuclear giant cells. ▪