A rich chemokine environment strongly enhances leukocyte migration and activities.
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.
Paoletti
Samantha
S
Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
Petkovic
Vibor
V
Sebastiani
Silvia
S
Danelon
M Gabriela
MG
Uguccioni
Mariagrazia
M
Gerber
Basil O
BO
D000818:Animals; D002460:Cell Line; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D018925:Chemokines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism / Q000494:pharmacology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; C110663:CXCL13 protein, human; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D046912:Multiprotein Complexes; D054400:Receptors, CCR7; D019707:Receptors, Chemokine