HCC-1, a novel chemokine from human plasma

• Published in: The Journal of experimental medicine Vol. 183; no. 1; pp. 295 - 299
• Main Authors: Schulz-Knappe, P, Mägert, H J, Dewald, B, Meyer, M, Cetin, Y, Kubbies, M, Tomeczkowski, J, Kirchhoff, K, Raida, M, Adermann, K, Kist, A, Reinecke, M, Sillard, R, Pardigol, A, Uguccioni, M, Baggiolini, M, Forssmann, W G
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 01.01.1996
• Subjects: Amino Acid Sequence; Base Sequence; Calcium - metabolism; Chemokine CCL4; Chemokines - chemistry; Chemokines - genetics; Chemokines - pharmacology; Chemokines, CC; Cloning, Molecular; Cytokines - pharmacology; DNA, Complementary - genetics; Humans; Kidney Failure, Chronic - blood; Macrophage Inflammatory Proteins; Mass Spectrometry; Molecular Sequence Data; Monocytes - drug effects; Monokines - genetics; Monokines - pharmacology; Sequence Analysis; Sequence Homology, Amino Acid; Tissue Distribution
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.183.1.295

A novel CC chemokine, HCC-1, was isolated from the hemofiltrate of patients with chronic renal failure. HCC-1 has a relative molecular mass of 8,673 and consists of 74 amino acids including four cysteines linked to disulfide bonds. HCC-1 cDNA was cloned from human bone marrow and shown to code for the mature protein plus a putative 19-residue leader sequence. Mature HCC-1 has sequence identity of 46% with macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, and 29-37% with the other human CC chemokines. Unlike MIP-1 alpha and the other CC chemokines, HCC-1 is expressed constitutively in several normal tissues (spleen, liver, skeletal and heart muscle, gut, and bone marrow), and is present at high concentrations (1-80 nM) in plasma. HCC-1 has weak activities on human monocytes and acts via receptors that also recognize MIP-1 alpha. It induced intracellular Ca2+ changes and enzyme release, but no chemotaxis, at concentrations of 100-1,000 nM, and was inactive on T lymphocytes, neutrophils, and eosinophil leukocytes. In addition, HCC-1 enhanced the proliferation of CD34+ myeloid progenitor cells. It was as effective as MIP-1 alpha, but about 100-fold less potent.