Identification of a blood-derived chemoattractant for neutrophils and lymphocytes as a novel CC chemokine, Regakine-1

Chemokines constitute a large family of chemotactic cytokines that selectiv ely attract different blood cell types. Although most inflammatory chemoatt ractants are only induced and released in the circulation during acute infe ction, a restricted number of CXC and CC chemokines are constitutively pres ent in normal plasma at high concentrations. Here, such a chemotactic prote in was purified to homogeneity from serum and fully identified as a novel C C chemokine by mass spectrometry and amino acid sequence analysis. The prot ein, tentatively designated Regakine-1, shows less than 50% sequence identi ty with any known chemokine. This novel CC chemokine chemoattracts both neu trophils and lymphocytes but not monocytes or eosinophils. Its modest chemo tactic potency but high blood concentration is similar to that of other che mokines present in the circulation, such as hemofiltrate CC chemokine-1, pl atelet factor-4, and beta -thromboglobulin. Regakine-1 did not induce neutr ophil chemokinesis, However, it synergized with the CXC chemokines interleu kin-8 and granulocyte chemotactic protein-2, and the CC chemokine monocyte chemotactic protein-3, resulting in an at least a 2-fold increase of the ne utrophil and lymphocyte chemotactic response, respectively. The biologic ef fects of homogeneous natural Regakine-1 were confirmed with chemically synt hesized chemokine. Like other plasma chemokines, it is expected that Regaki ne-1 plays a unique role in the circulation during normal or pathologic con ditions. (Blood, 2001;97:2197-2204) (C) 2001 by The American Society of Hem atology.