Recombinant Human CCL14a/HCC-1 Protein

HCC-1 (Hemofiltrate CC Chemokine-1) was originally isolated from the hemofiltrate of human patients with chronic renal failure (1). It belongs to the CC chemokine superfamily and has been designated CCL14a. HCC-1/CCL14a cDNA encodes a 93 amino acid (aa) residue  precursor with a 19 aa signal peptide that is cleaved to form the 74 aa secreted protein (aa 20-93). By alternative splicing, a second longer isoform named HCC-3/CCL14b, which includes sequences from exon 3, also exists (2). HCC-1/CCL14a is expressed constitutively in various normal tissues including spleen, liver, muscle, gut and bone marrow. It circulates at nanomolar concentrations in human plasma. Different post-translationally modified HCC-1/CCL14a, including O-glycosylated and N-terminally truncated variants of HCC-1/CCL14a, have been identified (3, 4). Whereas the 74 aa peptide is a weak CCR1 agonist, the proteolytically processed, truncated HCC-1/CCL14a (aa 28-93) is a highly potent agonist of CCR1, CCR5 and to a lesser extent, CCR3. HCC-1/CCL14a (aa 28-93) promotes chemotaxis of T lymphocytes, monocytes and eosinophils, and inhibits infection of M-tropic human immunodeficiency virus type 1. Activation of the HCC-1/CCL14a precursor to active peptide is mediated by the urokinase type plasminogen activator or plasmin (5).