In 1969, a forgettable Hollywood movie parodied the information overload that tourists experience when they visit several countries in the shortest time possible. Thirty years later, scientists who are interested in chemokines also find their heads spinning in response to a seemingly endless and rapid parade of newly discovered chemokines and receptors. In this issue, Struyf and colleagues (page 2197) introduce us to the newest member of this family of proteins, which they call Regakine-1 in honor of the Rega Institute of Leuven, Belgium, where the discovery occurred.
Chemokines are best known for their ability to attract specific leukocyte subsets, and like with any chemotactic factor, directionality is dictated by establishing a chemokine concentration gradient. Thus it is one of the particularly galling puzzles of chemokine biology that a small number of these proteins circulate at high concentrations in plasma. Regakine-1 is one of these. Struyf and colleagues purified it from bovine serum, and like another circulating chemokine, HCC-1 (CCL14), Regakine-1 is present at 100-300 ng/mL in bovine serum. It is a weak chemoattractant for neutrophils and T lymphocytes, but given its high ambient concentration, its role as a primary attractant for these cells seems unlikely. Instead, Struyf and colleagues show that it enhances chemotactic responses to suboptimal doses of more potent chemokines and other attractants. It may be that Regakine-1 circulates in order to enhance migratory responses of blood-borne leukocytes. Why nature would choose this route rather than simply enhancing the inherent efficacy of chemokine receptor signal transduction is a mystery (if, in fact, this is Regakine-1's function). Solving the conundrum posed by Regakine-1's high plasma concentration will be a fascinating problem and is likely to reveal unexpected opportunities for influencing leukocyte migration in health and disease. Meanwhile, like gawkers on a whirlwind tour, we must do our best to keep up with the changing scenery.
