Chemokines are important mediators of cell migration during
inflammation and normal leukocyte trafficking. Inflammatory
chemokines are induced in multiple cell types at sites of
infection. Here, we describe a novel bovine
CC chemokine, designated
regakine-1, that is constitutively present at high concentrations in plasma. Cloning of its gene revealed an expected two intron/three exon organization, with a rather long first intron. In addition to a 21-residue
signal peptide, the coding sequence corresponded to a 71-residue secreted
protein. However, the natural
regakine-1 protein missed the COOH-terminal
lysine residue.
Regakine-1 has only weak sequence similarity (<50% identical residues) with other animal or human
chemokines. Northern blot analysis demonstrated
regakine-1 RNA expression in spleen and lung. At physiological concentrations (30-100 ng/mL), natural 7.5 kDa
regakine-1 stimulated
gelatinase B release from neutrophils and chemoattracted immature myeloid HL-60 cells, as well as mature granulocytes.
Regakine-1 was more potent on human myeloid cells than the human plasma
CC chemokine hemofiltrate CC chemokine-1 (HCC-1). Moreover,
regakine-1 synergized with the bacterial
peptide N-
formylmethionylleucylphenylalanine (fMLP), yielding a 10-fold increase in neutrophil chemotactic response above their additive effect.
Regakine-1 did not compete with
interleukin-8 (IL-8) for binding to neutrophils, nor did it affect fMLP-induced calcium signaling, suggesting that
regakine-1 recognizes a different receptor. In view of its high constitutive plasma concentration,
regakine-1 is believed to recruit myeloid cells into the circulation, whereas its synergy with other neutrophil
chemoattractants suggests that it also enhances the inflammatory response to
infection.