A rich chemokine environment strongly enhances leukocyte migration and activities

• Published in: Blood 2005-05, Vol.105 (9), p.3405-3412
• Main Authors: Paoletti, Samantha, Petkovic, Vibor, Sebastiani, Silvia, Danelon, M.Gabriela, Uguccioni, Mariagrazia, Gerber, Basil O.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Line; Chemokine CCL19; Chemokine CCL21; Chemokine CXCL13; Chemokines - chemical synthesis; Chemokines - metabolism; Chemokines - pharmacology; Chemokines, CC - metabolism; Chemokines, CXC - physiology; Chemotaxis, Leukocyte - drug effects; Drug Synergism; Fundamental and applied biological sciences. Psychology; Humans; Inflammation; Mice; Molecular and cellular biology; Multiprotein Complexes - metabolism; Multiprotein Complexes - pharmacology; Receptors, CCR7; Receptors, Chemokine - agonists; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; Transfection
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-04-1648

The migration of leukocytes in immune surveillance and inflammation is largely determined by their response to chemokines. While the chemokine specificities and expression patterns of chemokine receptors are well defined, it is still a matter of debate how leukocytes integrate the messages provided by different chemokines that are concomitantly produced in physiologic or pathologic situations in vivo. We present evidence for a novel regulatory mechanism of leukocyte trafficking. Our data are consistent with a mode of action where CC-chemokine receptor 7 (CCR7) agonists and unrelated, nonagonist chemokines first form a heteromeric complex, in the presence of which the triggering of CCR7 can occur at a much lower agonist concentration. The increase is synergistic and can be evoked by many but not all chemokines. Chemokine-induced synergism might provide an amplification system in “chemokine-rich” tissues, rendering leukocytes more competent to respond to migratory cues.