Calprotectin (S100A8/S100A9), an Inflammatory Protein Complex from Neutrophils with a Broad Apoptosis-Inducing Activity

Calprotectin, a complex of two calcium-binding proteins that belong to the S100 protein family, is abundant in the cytosolic fraction of neutrophils. A high level of calprotectin reportedly exists in extracellular fluid during various inflammatory conditions, such as rheumatoid arthritis, cystic fibrosis and abscesses. However, the exact biological role(s) of the factor is now under investigation. We recently observed that neutrophils contain a factor that shows growth-inhibitory and apoptosis-inducing activities against various cell types including tumor cells and normal fibroblasts, and we identified that factor as calprotectin. The findings suggest that calprotectin exerts a regulatory activity in inflammatory processes through its effect on the survival or growth states of cells participating in the inflammatory reaction. It is also possible that calprotectin, at a high concentration, might have a deleterious effect on fibroblasts and influence the recovery of inflammatory tissue. Therefore, the protein factor may be a new drug target to control inflammatory reactions. We found that a few of the Amaryllidaceae alkaloids effectively inhibited the growth-inhibitory and apoptosis-inducing activities of calprotectin. In this article, we focus on the biological functions of calprotectin in extracellular fluids, focusing on its apoptosis-inducing activity.