HCC-2, a human chemokine: Gene structure, expression pattern, and biological activity

HCC-2, a human chemokine: Gene structure, expression pattern, and biological activity

^†Lower Saxony Institute for Peptide Research, D-30625 Hannover, Germany; and ^‡Theodor-Kocher Institute, University of Bern, CH-3012 Bern, Switzerland

Communicated by David L. Garbers, University of Texas Southwestern, Dallas, TX (received for review August 12, 1997)

Abstract

Cloning and sequencing of the upstream region of the gene of the CC chemokine HCC-1 led to the discovery of an adjacent gene coding for a CC chemokine that was named “HCC-2.” The two genes are separated by 12-kbp and reside in a head-to-tail orientation on chromosome 17. At variance with the genes for HCC-1 and other human CC chemokines, which have a three-exon-two-intron structure, the HCC-2 gene consists of four exons and three introns. Expression of HCC-2 and HCC-1 as studied by Northern analysis revealed, in addition to the regular, monocistronic mRNAs, a common, bicistronic transcript. In contrast to HCC-1, which is expressed constitutively in numerous human tissues, HCC-2 is expressed only in the gut and the liver. HCC-2 shares significant sequence homology with CKβ8 and the murine chemokines C10, CCF18/MRP-2, and macrophage inflammatory protein 1γ, which all contain six instead of four conserved cysteines. The two additional cysteines of HCC-2 form a third disulfide bond, which anchors the COOH-terminal domain to the core of the molecule. Highly purified recombinant HCC-2 was tested on neutrophils, eosinophils, monocytes, and lymphocytes and was found to exhibit marked functional similarities to macrophage inflammatory protein 1α. It is a potent chemoattractant and inducer of enzyme release in monocytes and a moderately active attractant for eosinophils. Desensitization studies indicate that HCC-2 acts mainly via CC chemokine receptor CCR1.

Footnotes

↵ * A.P. and U.F. contributed equally to this work.
↵ § To whom reprint requests should be addressed. e-mail: 100446.463{at}compuserve.com.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. Z70292).
ABBREVIATIONS:

MIP,

macrophage inflammatory protein;

MCP,

monocyte chemoattractant protein;

[Ca2+]i,

cytosolic free calcium concentration;

CCR,

CC chemokine receptor;

I,

inosine nucleotide;

r,

recombinant;

EST,

expressed sequence tag;

CC,

chemokine type CC