S100A8: emerging functions and regulation

The functional importance of members of the S100 Ca2+-binding protein famil y is becoming apparent. Murine (m)S100A8 (initially named CP-10) is a poten t chemoattractant (10(-13) to 10(-11) M) for myeloid cells and the chemotac tic activity of other S100s has since been reported, suggesting a new class of chemoattractants. Murine S100A8 has been associated with a number of ac ute and chronic inflammatory conditions including bacterial infection, athe rogenesis, and cystic fibrosis, It is expressed constitutively with S100A9 in neutrophils and is regulated by inflammatory stimulants in macrophages a nd microvascular endothelial cells. The lack of co-expression of S100A9 wit h S100A8 in activated macrophages suggests distinct functions for the prote ins expressed by different cell types. Glucocorticoids up-regulate inductio n of mS100A8 by inflammatory mediators, and its exquisite sensitivity to ox idation suggests that it may protect against oxidative tissue damage, Inact ivation of the mS100A8 gene is embryonic lethal, providing the first eviden ce for non-redundant function of a member of the S100 gene family, S100A8 m ay have au immunoregulatory role by contributing to the regulation of fetal -maternal interactions. It may play a protective role and its absence may a llow infiltration by maternal cells, a process eventually manifesting as re sorption, This review focuses on the variety of emerging functions attribut ed to murine S100A8, a protein implicated in embryogenesis, growth, differe ntiation, and immune and inflammatory processes.