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MIP-3alpha induces human eosinophil migration and activation of the mitogen-activated protein kinases (p42/p44 MAPK)

S K Sullivan1, D A McGrath, F Liao

  • 1Department of Immunology, Neurocrine Biosciences Inc., San Diego, California 92121, USA.

Journal of Leukocyte Biology
|October 26, 1999
PubMed

Insights

Macrophage inflammatory protein-3alpha (MIP-3alpha) induces human eosinophil migration via pertussis-toxin-sensitive pathways. MIP-3alpha activates mitogen-activated protein kinases (MAPK) and phosphoinositide 3-kinase signaling in eosinophils.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Macrophage inflammatory protein-3alpha (MIP-3alpha) is a CC chemokine with incompletely characterized biological effects.
  • Eosinophils play a role in inflammatory and allergic responses.

Purpose of the Study:

  • To characterize the biological effects of MIP-3alpha on human eosinophils.
  • To investigate the signaling pathways involved in MIP-3alpha-induced eosinophil responses.

Main Methods:

  • Human eosinophils were used to assess migration in response to MIP-3alpha.
  • Reverse transcriptase-polymerase chain reaction (RT-PCR) and FACS analysis were employed to detect MIP-3alpha receptor (CCR-6) expression.
  • Intracellular calcium mobilization and mitogen-activated protein kinase (MAPK) phosphorylation were measured to analyze signal transduction.

Main Results:

  • Human eosinophils demonstrated MIP-3alpha-induced, pertussis-toxin-sensitive migration.
  • CCR-6 mRNA and surface expression were detected on eosinophils.
  • MIP-3alpha induced dose-dependent increases in intracellular calcium and MAPK phosphorylation, linked to phosphoinositide 3-kinase (PI3K) pathway.

Conclusions:

  • MIP-3alpha regulates multiple signaling pathways in eosinophils, including calcium mobilization and PI3K.
  • MAPK activation by MIP-3alpha is a significant pathway for inducing eosinophil migration.

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