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Ionomycin causes activation of p38 and p42/44 mitogen-activated protein kinases in human neutrophils

D J Elzi1, A J Bjornsen, T MacKenzie

  • 1Bonfils Blood Center, Denver, CO 80230, USA.

American Journal of Physiology. Cell Physiology
|June 13, 2001
PubMed

Insights

Calcium influx is crucial for activating p38 and p42/44 MAP kinases in neutrophils, which are key components of the immune response. This study highlights calcium

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Receptor-linked agents activate NADPH oxidase in polymorphonuclear neutrophils (PMNs), affecting cytosolic calcium (Ca2+) and mitogen-activated protein (MAP) kinases.
  • The precise role of Ca2+ in activating p38 and p42/44 MAP kinases remains to be fully elucidated.

Purpose of the Study:

  • To investigate the role of Ca2+ in the activation of p38 and p42/44 MAP kinases during PMN oxidase activation.
  • To examine the effects of the Ca2+-selective ionophore ionomycin on PMN oxidase priming and activation.

Main Methods:

  • Utilized the Ca2+-selective ionophore ionomycin to induce changes in cytosolic Ca2+ in PMNs.
  • Assessed PMN oxidase activity, MAP kinase phosphorylation (p38, p42/44), and substrate phosphorylation (ATF-2, Elk-1).
  • Employed specific MAP kinase antagonists (SB-203580, PD-98059) and Ca2+ chelation techniques.

Main Results:

  • Ionomycin triggered a rapid increase in cytosolic Ca2+ via store release and influx, leading to PMN oxidase activation and priming.
  • p38 MAP kinase activation correlated with ionomycin concentrations that primed or activated the oxidase, while p42/44 MAP kinase activation occurred at higher concentrations.
  • SB-203580 inhibited ionomycin-induced oxidase activation and tyrosine phosphorylation, whereas PD-98059 had no effect.
  • Cytosolic Ca2+ chelation blocked ionomycin-induced p38 MAP kinase activation, and extracellular Ca2+ chelation inhibited p42/44 MAP kinase activation.

Conclusions:

  • Changes in cytosolic Ca2+ are essential for the activation of p38 and p42/44 MAP kinases in PMNs.
  • p38 MAP kinase activation is critically dependent on intracellular Ca2+ mobilization.
  • Extracellular Ca2+ influx plays a significant role in the activation of p42/44 MAP kinase.

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