CCL3 (MIP-1α) induces in vitro migration of GM-CSF-primed human neutrophils via CCR5-dependent activation of ERK 1/2

Luciano Ottonello, Fabrizio Montecucco, Maria Bertolotto, Nicoletta Arduino, Marina Mancini, Anna Corcione, Vito Pistoia, Franco Dallegri

Research output: Contribution to journalArticle


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 languageEnglish
Pages (from-to)355-363
Number of pages9
JournalCellular Signalling
Issue number3
Publication statusPublished - Mar 2005



  • Chemokines
  • Chemotaxis
  • GM-CSF
  • Inflammation
  • Neutrophil
  • Signal transduction

ASJC Scopus subject areas

  • Cell Biology

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