CK beta-11/macrophage inflammatory protein-3 beta/EBI1-ligand chemokine is an efficacious chemoattractant for T and B cells.
We examined the functional properties of CK beta-11/MIP-3 beta/ELC, a recently reported CC chemokine that specifically binds to a chemokine receptor, EBI1/BLR2/CCR7. CK beta-11/MIP-3 beta/ELC is distantly related to other CC and CXC chemokines in primary amino acid sequence structure. Recombinant human CK beta-11/MIP-3 beta/ELC expressed from a mammalian cell system showed potent chemotactic activity for T cells and B cells but not for granulocytes and monocytes. An optimal concentration 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 derived factor 1 (SDF-1), a highly efficacious CXC chemokine. CK beta-11/MIP-3 beta/ELC equally attracted naive CD45RA+ and memory type CD45RO+ T cells. CK beta-11/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 chemoattractant for B cells than MIP-1 alpha, a known B cell chemoattractant. CK beta-11/MIP-3 beta/ELC induced actin polymerization in lymphocytes, and chemotaxis was completely blocked by pertussis toxin showing its receptor, 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, which could be desensitized by SDF-1, suggesting possible cross-regulation in their signaling. Human CK beta-11/MIP-3 beta/ELC attracted murine splenocytes suggesting functional conservation of CK beta-11/MIP-3 beta/ELC between human and mouse. The efficacy of chemoattraction by CK beta-11/MIP-3 beta/ELC and tissue expression of its mRNA suggest that 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 organs.
Kim
C H
CH
Department of Microbiology/Immunology, The Walther Oncology Center, Indiana University School of Medicine, Indianapolis 46202, USA.
Pelus
L M
LM
White
J R
JR
Applebaum
E
E
Johanson
K
K
Broxmeyer
H E
HE
D000199:Actins / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D054415:Chemokine CCL19; D018925:Chemokines / Q000502:physiology; D019742:Chemokines, CC; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D008024:Ligands; D019402:Macrophage Inflammatory Proteins / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000502:physiology; D037342:Pertussis Toxin; D011108:Polymers / Q000378:metabolism; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface / Q000502:physiology*; D019707:Receptors, Chemokine; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000199:Actins; C515460:CCL19 protein, human; C515370:CCR7 protein, human; C515461:Ccl19 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D018925:Chemokines; D019742:Chemokines, CC; D008024:Ligands; D019402:Macrophage Inflammatory Proteins; D011108:Polymers; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D002118:Calcium