REGAKINE-1

摘要

Chemokines constitute a large family of chemotactic cytokines which selectively attract different blood cell types. Although most inflammatory chemoattractants are only induced and released in the circulation during acute infection, a restricted number of CXC and CC chemokines is constitutively present in normal plasma at high concentrations. Present invention involves a chemotactic protein that was isolated from serum and fully identified as a novel CC chemokine by mass spectrometry and amino acid sequence analysis. The protein, tentatively designated Regakine-1, shows less than 50% sequence identity with any known chemokine. This novel CC chemokine chemoattracts both neutrophils and lymphocytes but not monocytes or eosinophils. Its modest chemotactic potency, but high blood concentration are similar to those of other chemokines present in the circulation, such as hemofiltrate CC chemokine-1 (HCC-1), platelet factor-4 (PF-4) and &bgr;-thromboglobulin (&bgr;-TG). Regakine-1 did not induce neutrophil chemokinesis. However, it synergized with fMLP, the CXC chemokines interleukin-8 (IL-8) and granulocyte chemotactic protein-2 (GCP-2) and the CC chemokine monocyte chemotactic protein-3 (MCP-3), resulting in an at least 2-fold increase of the neutrophil and lymphocyte chemotactic response, respectively. The biological effects of homogeneous natural Regakine-1 were confirmed with chemically synthesized chemokine. Like other plasma chemokines, it is expected that Regakine-1 plays a unique role in the circulation during normal or pathological conditions.