Abstract
CCL3 (MIP-1α), a prototype of CC chemokines, is a potent chemoattractant toward human neutrophils pre-treated with GM-CSF for 15 min. GM-CSF-treated neutrophils migrate also to the selective CCR5 agonist CCL4 ?MIP-1β). CCL3- and CCL4-triggered migration of GM-CSF-primed neutrophils was inhibited by the CCR5 antagonist TAK-779. Accordingly, freshly isolated neutrophils express CCR5. Extracellular signal-regulated kinases (ERK)-1/2 and p38 mitogen-activated protein kinase (MAPK) inhibitors blocked CCL3-induced migration of GM-CSF-primed neutrophils. When the activation of ERK-1/2 and p38 MAPK by CCL3 and the classical neutrophilic chemokine CXCL8 (IL-8) were compared, both the chemokines were capable of activating p38 MAPK. On the contrary, whereas both ERK-1 and ERK-2 were activated by CXCL8, no ERK-1 band was detectable after CCL3 triggering. Finally, neutrophil pre-treatment with GM-CSF activated both ERK-1 and ERK-2. This suggests that by activating ERK-1, GM-CSF renders neutrophils rapidly responsive to CCL3 stimulation throughout CCR5 which is constitutively expressed on the cell surface.
| Original language | English |
|---|---|
| Pages (from-to) | 355-363 |
| Number of pages | 9 |
| Journal | Cellular Signalling |
| Volume | 17 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2005 |
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Keywords
- Chemokines
- Chemotaxis
- GM-CSF
- Inflammation
- Neutrophil
- Signal transduction
ASJC Scopus subject areas
- Cell Biology
Cite this
CCL3 (MIP-1α) induces in vitro migration of GM-CSF-primed human neutrophils via CCR5-dependent activation of ERK 1/2. / Ottonello, Luciano; Montecucco, Fabrizio; Bertolotto, Maria; Arduino, Nicoletta; Mancini, Marina; Corcione, Anna; Pistoia, Vito; Dallegri, Franco.
In: Cellular Signalling, Vol. 17, No. 3, 03.2005, p. 355-363.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CCL3 (MIP-1α) induces in vitro migration of GM-CSF-primed human neutrophils via CCR5-dependent activation of ERK 1/2
AU - Ottonello, Luciano
AU - Montecucco, Fabrizio
AU - Bertolotto, Maria
AU - Arduino, Nicoletta
AU - Mancini, Marina
AU - Corcione, Anna
AU - Pistoia, Vito
AU - Dallegri, Franco
PY - 2005/3
Y1 - 2005/3
N2 - CCL3 (MIP-1α), a prototype of CC chemokines, is a potent chemoattractant toward human neutrophils pre-treated with GM-CSF for 15 min. GM-CSF-treated neutrophils migrate also to the selective CCR5 agonist CCL4 ?MIP-1β). CCL3- and CCL4-triggered migration of GM-CSF-primed neutrophils was inhibited by the CCR5 antagonist TAK-779. Accordingly, freshly isolated neutrophils express CCR5. Extracellular signal-regulated kinases (ERK)-1/2 and p38 mitogen-activated protein kinase (MAPK) inhibitors blocked CCL3-induced migration of GM-CSF-primed neutrophils. When the activation of ERK-1/2 and p38 MAPK by CCL3 and the classical neutrophilic chemokine CXCL8 (IL-8) were compared, both the chemokines were capable of activating p38 MAPK. On the contrary, whereas both ERK-1 and ERK-2 were activated by CXCL8, no ERK-1 band was detectable after CCL3 triggering. Finally, neutrophil pre-treatment with GM-CSF activated both ERK-1 and ERK-2. This suggests that by activating ERK-1, GM-CSF renders neutrophils rapidly responsive to CCL3 stimulation throughout CCR5 which is constitutively expressed on the cell surface.
AB - CCL3 (MIP-1α), a prototype of CC chemokines, is a potent chemoattractant toward human neutrophils pre-treated with GM-CSF for 15 min. GM-CSF-treated neutrophils migrate also to the selective CCR5 agonist CCL4 ?MIP-1β). CCL3- and CCL4-triggered migration of GM-CSF-primed neutrophils was inhibited by the CCR5 antagonist TAK-779. Accordingly, freshly isolated neutrophils express CCR5. Extracellular signal-regulated kinases (ERK)-1/2 and p38 mitogen-activated protein kinase (MAPK) inhibitors blocked CCL3-induced migration of GM-CSF-primed neutrophils. When the activation of ERK-1/2 and p38 MAPK by CCL3 and the classical neutrophilic chemokine CXCL8 (IL-8) were compared, both the chemokines were capable of activating p38 MAPK. On the contrary, whereas both ERK-1 and ERK-2 were activated by CXCL8, no ERK-1 band was detectable after CCL3 triggering. Finally, neutrophil pre-treatment with GM-CSF activated both ERK-1 and ERK-2. This suggests that by activating ERK-1, GM-CSF renders neutrophils rapidly responsive to CCL3 stimulation throughout CCR5 which is constitutively expressed on the cell surface.
KW - Chemokines
KW - Chemotaxis
KW - GM-CSF
KW - Inflammation
KW - Neutrophil
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=9644275452&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=9644275452&partnerID=8YFLogxK
U2 - 10.1016/j.cellsig.2004.08.002
DO - 10.1016/j.cellsig.2004.08.002
M3 - Article
VL - 17
SP - 355
EP - 363
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 3
ER -