TY - JOUR
T1 - Synergy-inducing chemokines enhance CCR2 ligand activities on monocytes
AU - Kuscher, Katrin
AU - Danelon, Gabriela
AU - Paoletti, Samantha
AU - Stefano, Luisa
AU - Schiraldi, Milena
AU - Petkovic, Vibor
AU - Locati, Massimo
AU - Gerber, Basil O.
AU - Uguccioni, Mariagrazia
PY - 2009
Y1 - 2009
N2 - The migration of monocytes to sites of inflammation is largely determined by their response to chemokines. Although the chemokine specificities and expression patterns of chemokine receptors are well defined, it is still a matter of debate how cells integrate the messages provided by different chemokines that are concomitantly produced in physiological or pathological situations in vivo. We present evidence for one regulatory mechanism of human monocyte trafficking. Monocytes can integrate stimuli provided by inflammatory chemokines in the presence of homeostatic chemokines. In particular, migration and cell responses could occur at much lower concentrations of the CCR2 agonists, in the presence of chemokines (CCL19 and CCL21) that per se do not act on monocytes. Binding studies on CCR2+ cells showed that CCL19 and CCL21 do not compete with the CCR2 agonist CCL2. Furthermore, the presence of CCL19 or CCL21 could influence the degradation of CCL2 and CCL7 on cells expressing the decoy receptor D6. These findings disclose a new scenario to further comprehend the complexity of chemokine-based monocyte trafficking in a vast variety of human inflammatory disorders.
AB - The migration of monocytes to sites of inflammation is largely determined by their response to chemokines. Although the chemokine specificities and expression patterns of chemokine receptors are well defined, it is still a matter of debate how cells integrate the messages provided by different chemokines that are concomitantly produced in physiological or pathological situations in vivo. We present evidence for one regulatory mechanism of human monocyte trafficking. Monocytes can integrate stimuli provided by inflammatory chemokines in the presence of homeostatic chemokines. In particular, migration and cell responses could occur at much lower concentrations of the CCR2 agonists, in the presence of chemokines (CCL19 and CCL21) that per se do not act on monocytes. Binding studies on CCR2+ cells showed that CCL19 and CCL21 do not compete with the CCR2 agonist CCL2. Furthermore, the presence of CCL19 or CCL21 could influence the degradation of CCL2 and CCL7 on cells expressing the decoy receptor D6. These findings disclose a new scenario to further comprehend the complexity of chemokine-based monocyte trafficking in a vast variety of human inflammatory disorders.
KW - Chemokine receptors
KW - Chemokines
KW - Monocytes
KW - Synergism
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U2 - 10.1002/eji.200838906
DO - 10.1002/eji.200838906
M3 - Article
C2 - 19291700
AN - SCOPUS:65449187994
VL - 39
SP - 1118
EP - 1128
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 4
ER -