Hemofiltrate CC chemokines with unique biochemical properties: HCC-1/CCL14a and HCC-2/CCL15

The hemofiltrate CC chemokines CCL14a (formerly HCC-I), CCL14b (formerly HC C-3), and CCL15 (formerly HCC-2) are encoded by mono- as well as bicistroni c transcripts from a tandem gene arrangement on human chromosome 17q11.2. T he transcription and splicing into several mono- and bicistronic transcript s of this gene complex are unique for human genes. No corresponding mechani sm is known in nonprimate mammalian species such as mice and rats. The extr emely high concentration of CCL14a in human Plasma is exceptional for chemo kines and led to the identification of this chemokine. Several molecular fo rms of CCL14a have been isolated and investigated. The mature propeptide CC L14a(1-74) is a low-affinity agonist of CCR1 which is converted to a high-a ffinity agonist of CCR1 and CCR5 on proteolytic processing by serine protea ses. In contrast, CCL15 is characterized using molecular forms deduced from the mRNA/cDNA and shown to activate cells via CCR1 and CCR3, also dependen t on the amino-terminal length. Hemofiltrate CC chemokines are chemoattract ants for different types of leukocytes including monocytes, eosinophils, T cells, dendritic cells, and neutrophils. In this review, we emphasize the g enomic organization, expression patterns, and biochemical properties of CCL 14a, CCL14b, and CCL15. We report results of significance for the developme nt of therapeutic strategies, especially concerning HIV infection and infla mmatory diseases.