CK-BETA-11 MACROPHAGE INFLAMMATORY PROTEIN-3-BETA EBI1-LIGAND CHEMOKINE IS AN EFFICACIOUS CHEMOATTRACTANT FOR T-CELL AND B-CELL

We examined the functional properties of CK beta-11/MIP . 3 beta/ELC, a recently reported CC chemokine that specifically binds to a chemokin e receptor, EBI1/BLR2/CCR7. CK beta 11/MIP-3 beta/ELC is distantly rel ated to other CC and CXC chemokines in primary amino acid sequence str ucture, Recombinant human CK beta-11/MIP-3 beta/ELC expressed from a m ammalian cell system showed potent chemotactic activity for T cells an d B cells but not for granulocytes and monocytes, An optimal concentra tion of CK beta-11/MIP-3 beta/ELC attracted most input T cells within 3 h, a chemotactic activity comparable with that of stromal cell deriv ed factor 1 (SDF-1), a highly efficacious CXC chemokine. CK beta-11/MI P-3 beta/ELC equally attracted naive CD45RA(+) and memory type CD45RO( +) T cells, CK beta/MIP-3 beta/ELC also strongly attracted both CD4(+) and CD8(+) T cells, but the attraction for CD4(+) T cells was greater , CK beta-11/MIP-3 beta/ELC was also a more efficacious chemoattractan t for B cells than MIP-1 alpha, a known B cell chemoattractant, CK bet a-11/MIP-3 beta/ELC induced actin polymerization in lymphocytes, and c hemotaxis was completely blocked by pertussis toxin showing its recept or, most likely EBI1/BLR2/CCR7, is coupled to a G(alpha i) protein, CK beta-11/MIP-3 beta/ELC induced calcium mobilization in lymphocytes, w hich could be desensitized by SDF-1, suggesting possible cross-regulat ion in their signaling, Human CK beta-11/MIP-3 beta/ELC attracted muri ne splenocytes suggesting functional conservation of CK beta-11/MIP-3 beta/ELC between human and mouse, The efficacy of chemoattraction by C K beta-11/MIP-3 beta/ELC and tissue expression of its mRNA suggest tha t CK beta-11/MIP-3 beta/ELC may be important in trafficking of T cells in thymus, and T cell and B cell migration to secondary lymphoid orga ns.