MIP-3 alpha, also known as LARC (Liver and Activation-regulated Chemokine) and Exodus, is one of many novel beta chemokines identified through bioinformatics. Mouse MIP-3 alpha cDNA encodes a 97 amino acid residue precursor protein with a 27 aa residue putative signal peptide that is predicted to be cleaved to form the 70 aa residue mature secreted protein. MIP-3 alpha is distantly related to other beta chemokines (20-28% aa sequence identity). Mouse MIP-3 alpha shares approximately 71% and 63% amino acid sequence homology with rat and human MIP-3 alpha, respectively.
MIP-3 alpha has been shown to be expressed predominantly in lymph nodes, appendix, PBL, fetal liver, fetal lung, and epithelial cells of intestinal tissues. The expression of MIP-3 alpha is strongly up-regulated by inflammatory signals and down-regulated by the anti-inflammatory cytokine IL-10. Synthetic or recombinant MIP-3 alpha has been shown to be chemotactic for lymphocytes and dendritic cells, and inhibits proliferation of myeloid progenitors in colony formation assays. MIP-3 alpha has now been shown to be a unique functional ligand for CCR6 (previously referred to as GPR-CY4, CKR-L3, or STRL22 orphan receptor), a chemokine receptor that is selectively and highly expressed in human dendritic cells derived from CD34+ cord blood precursors.
