S100A8: emerging functions and regulation

The functional importance of members of the S100 Ca2+-binding protein family is becoming apparent. Murine (m)S100A8 (initially named CP-10) is a potent chemoattractant (10(-13) to 10(-11) M) for myeloid cells and the chemotactic activity of other S100s has since been reported, suggesting a new class of chemoattractants. Murine S100A8 has been associated with a number of acute and chronic inflammatory conditions including bacterial infection, atherogenesis, and cystic fibrosis. It is expressed constitutively with S100A9 in neutrophils and is regulated by inflammatory stimulants in macrophages and microvascular endothelial cells. The lack of co-expression of S100A9 with S100A8 in activated macrophages suggests distinct functions for the proteins expressed by different cell types. Glucocorticoids up-regulate induction of mS100A8 by inflammatory mediators, and its exquisite sensitivity to oxidation suggests that it may protect against oxidative tissue damage. Inactivation of the mS100A8 gene is embryonic lethal, providing the first evidence for non-redundant function of a member of the S100 gene family. S100A8 may have an immunoregulatory role by contributing to the regulation of fetal-maternal interactions. It may play a protective role and its absence may allow infiltration by maternal cells, a process eventually manifesting as resorption. This review focuses on the variety of emerging functions attributed to murine S100A8, a protein implicated in embryogenesis, growth, differentiation, and immune and inflammatory processes.