title: Gene cloning of a new plasma CC chemokine, activating and attracting myeloid cells in synergy with other chemoattractants.
abstract: 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.
authors.affiliation: Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Struyf
authors.forename: G
authors.initials: G
authors.lastname: Stoops
authors.forename: E
authors.initials: E
authors.lastname: Van Coillie
authors.forename: M
authors.initials: M
authors.lastname: Gouwy
authors.forename: E
authors.initials: E
authors.lastname: Schutyser
authors.forename: J P
authors.initials: JP
authors.lastname: Lenaerts
authors.forename: P
authors.initials: P
authors.lastname: Fiten
authors.forename: I
authors.initials: I
authors.lastname: Van Aelst
authors.forename: P
authors.initials: P
authors.lastname: Proost
authors.forename: G
authors.initials: G
authors.lastname: Opdenakker
authors.forename: J
authors.initials: J
authors.lastname: Van Damme
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002417:Cattle; D002460:Cell Line; D019742:Chemokines, CC / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D002634:Chemotaxis, Leukocyte; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism
chemical_list: D019742:Chemokines, CC; D018076:DNA, Complementary; C426232:regakine 1; D009240:N-Formylmethionine Leucyl-Phenylalanine