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Presence of the M-type sPLA(2) receptor on neutrophils and its role in elastase release and adhesion

Christopher C Silliman1, Ernest E Moore, Garret Zallen

  • 1Bonfils Blood Center, Department of Pediatrics, University of Colorado School of Medicine, Denver, CO 80262, USA.

American Journal of Physiology. Cell Physiology
|September 13, 2002
PubMed

Insights

Polymorphonuclear neutrophils (PMNs) possess a membrane receptor for secretory phospholipase A2 (sPLA2). This receptor activates p38 MAPK, influencing PMN responses like elastase release and adhesion.

Area of Science:

  • Immunology
  • Biochemistry
  • Cell Biology

Background:

  • Secretory phospholipase A2 (sPLA2) is known to stimulate polymorphonuclear neutrophils (PMNs).
  • The recent discovery of sPLA2 receptors (sPLA2-R) suggests a potential receptor-mediated mechanism for sPLA2-induced PMN activation.

Purpose of the Study:

  • To investigate the hypothesis that sPLA2 stimulates PMNs via a specific receptor.
  • To characterize the binding and functional consequences of sPLA2-receptor interaction on PMNs.

Main Methods:

  • Scatchard analysis to determine sPLA2 ligand binding kinetics.
  • Immunohistochemistry using an antibody against the M-type sPLA2-R to assess receptor presence and localization.
  • Treatment of PMNs with active and inactive sPLA2 (types IA, IB, IIA) to measure elastase release and adhesion.
  • Assessment of p38 MAPK activation and the effect of its inhibition on PMN responses.

Main Results:

  • A specific sPLA2 receptor (sPLA2-R) was identified on PMNs, with saturation at 2.77 fM and a K(d) of 167 pM for inactive sPLA2-IB.
  • sPLA2-R immunoreactivity was detected at 185 kDa and localized to the cell membrane.
  • Inactive sPLA2-IB activated p38 MAPK, which was crucial for subsequent elastase release.
  • sPLA2-IB induced elastase release independently of its enzymatic activity, while sPLA2-IA required enzymatic activity.
  • sPLA2-IB and sPLA2-IIA promoted PMN adhesion.

Conclusions:

  • PMNs express a membrane-bound M-type sPLA2 receptor.
  • This receptor mediates sPLA2-induced PMN activation, partly through the activation of the p38 MAPK pathway.
  • The findings elucidate a novel mechanism of PMN regulation by sPLA2.

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