MIP-1 gamma: molecular cloning, expression and biological activities of a novel CC chemokine that is constitutively secreted in vivo.

We have identified a novel CC chemokine family member, herein termed MIP-l-gamma in view of its similarity to existing members of the MIP-1 group. The murine protein has a predicted length of 100 amino acids. Like MIP-1-alpha, recombinant MIP-1-gamma acts as a pyrogen when administered intracerebroventricularly. MIP-1-gamma and MIP-1-alpha engage the same high-affinity receptor on neutrophils, activating calcium release within seconds following cell contact. Pretreatment with either chemokine abolishes responses to the other, and to itself, suggesting utilization of a common signaling pathway. However, unlike MIP-1-alpha or any of the other CC chemokines, MIP-1-gamma is expressed constitutively by a wide variety of tissues, and circulates in the blood of healthy mice at concentrations of approximately 1 mu-g/ml (90 nM). It would therefore be predicted that MIP-1-gamma occupies most of the CC chemokine receptors that exist in the intravascular compartment. As such it might, under normal circumstances, markedly influence responses to the inducible CC chemokines.