Molecular cloning and expression of the murine RANTES cytokine: structural and functional conservation between mouse and man

Abstract

The infiltration and activation of monocytes is a hallmark of chronic inflammation, including that associated with a variety of disease states such as rheumatoid arthritis, atherosclerosis, and various autoimmune conditions. Recently, a family of small molecular mass proteins has been described which appear to have inflammatory properties, including chemoattractant effects on monocytes. We report here on the molecular cloning, characterization, and functional expression of mu RANTES, a new murine member of this family. mu RANTES expressed in a mammalian expression system is an approximately 8-kDa protein exhibiting immune cross-reactivity with a rabbit polyclonal antiserum generated against human RANTES. Boyden chamber chemotaxis experiments reveal some lack of species specificity in monocyte chemoattractant potential, as recombinant mu RANTES attracts human monocytes in a dose-dependent fashion in vitro. mu RANTES and its human homolog share approximately 85% amino acid identity, a higher level of conservation than that seen with any other species homologs in this cytokine family, and second only to transforming growth factor-beta among reported immune cytokines.