When certain hostile agents breach the armor of a horseshoe crab, soldiers in an ancient immune defense system throw themselves around the invaders, marking the intruders for destruction and elimination. This dramatic and bizarre behavior of the ancient defender molecules known as a2-macroglobulin is described in a recent issue of the Journal of Biological Chemistry by Peter Armstrong, a UC Davis professor of molecular and cellular biology; James Quigley, a professor of pathology at the State University of New York at Stony Brook; and UC Davis postdoctoral fellow Ralph Melchior. The defender a2-macroglobulin targets "proteases" -- enzymes released by invading bacteria and parasites that destroy proteins of the host. Without these defenders, the blood system couldn't tell the difference between a benign native protein and the potentially dangerous proteases. In humans, inadequate regulation of proteases contributes to diseases such as arthritis and emphysema. The pathogen-fighting mechanism described by Armstrong and his colleagues appears to have evolved at least one-half billion years ago, and is still found in a diverse variety of animals, including humans, arthropods and mollusks. Potential applications of this research include a better general understanding of immunity; improved veterinary care for aquaculturally important arthropods, such as shrimp and lobster; and more effective biological weapons for agricultural pests and disease-transmitting organisms, Armstrong says.