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

Area of Science:

• Immunology and Molecular Biology
• Gene structure and expression
• Chemokine function

Background:

• The CC chemokine HCC-1 gene's upstream region was analyzed, leading to the identification of a novel adjacent gene, HCC-2.
• HCC-2 shares structural and functional similarities with other CC chemokines but possesses a unique four-exon, three-intron gene structure.

Purpose of the Study:

• To characterize the newly discovered HCC-2 gene and its encoded chemokine.
• To investigate the expression pattern, structure, and functional activity of HCC-2.
• To determine the receptor through which HCC-2 exerts its effects.

Main Methods:

• Gene cloning and sequencing
• Northern blot analysis for gene expression studies
• Functional assays using purified recombinant HCC-2 on various immune cells
• Desensitization studies to identify the chemokine receptor involved

Main Results:

• HCC-2 gene is located 12-kbp downstream of HCC-1 on chromosome 17 in a head-to-tail orientation.
• HCC-2 exhibits a distinct gene structure (four exons, three introns) compared to other CC chemokines.
• A common bicistronic transcript for both HCC-1 and HCC-2 was observed.
• HCC-2 expression is restricted to the gut and liver, unlike the constitutive expression of HCC-1.
• Recombinant HCC-2 functions as a potent chemoattractant and enzyme release inducer for monocytes and a moderate attractant for eosinophils.
• HCC-2 primarily signals through the CC chemokine receptor CCR1.

Conclusions:

• HCC-2 represents a novel CC chemokine with restricted tissue expression and specific chemoattractant properties.
• The unique gene structure and functional characteristics of HCC-2 highlight the diversity within the CC chemokine family.
• HCC-2's activity via CCR1 suggests its potential role in inflammatory processes within the gut and liver.