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

Am J Physiol Cell Physiol. 2002 Oct;283(4):C1102-13. doi: 10.1152/ajpcell.00608.2001.

Abstract

Secretory phospholipase A(2) (sPLA(2)) produces lipids that stimulate polymorphonuclear neutrophils (PMNs). With the discovery of sPLA(2) receptors (sPLA(2)-R), we hypothesize that sPLA(2) stimulates PMNs through a receptor. Scatchard analysis was used to determine the presence of a sPLA(2) ligand. Lysates were probed with an antibody to the M-type sPLA(2)-R, and the immunoreactivity was localized. PMNs were treated with active and inactive (+EGTA) sPLA(2) (1-100 units of enzyme activity/ml, types IA, IB, and IIA), and elastase release and PMN adhesion were measured. PMNs incubated with inactive, FITC-linked sPLA(2)-IB, but not sPLA(2)-IA, demonstrated the presence of a sPLA(2)-R with saturation at 2.77 fM and a K(d) of 167 pM. sPLA(2)-R immunoreactivity was present at 185 kDa and localized to the membrane. Inactive sPLA(2)-IB activated p38 MAPK, and p38 MAPK inhibition attenuated elastase release. Active sPLA(2)-IA caused elastase release, but inactive type IA did not. sPLA(2)-IB stimulated elastase release independent of activity; inactive sPLA(2)-IIA partially stimulated PMNs. sPLA(2)-IB and sPLA(2)-IIA caused PMN adhesion. We conclude that PMNs contain a membrane M-type sPLA(2)-R that activates p38 MAPK.

MeSH terms

  • Binding, Competitive / drug effects
  • Calcium / metabolism
  • Cell Adhesion / physiology
  • Cell Membrane / metabolism
  • Cell Separation
  • Chelating Agents / metabolism
  • Chelating Agents / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Flow Cytometry
  • Fluorescent Dyes
  • Group IB Phospholipases A2
  • Group II Phospholipases A2
  • Humans
  • Leukocyte Elastase / metabolism*
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Phospholipases A / antagonists & inhibitors
  • Phospholipases A / pharmacology
  • Receptors, Cell Surface / physiology*
  • Receptors, Phospholipase A2
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Chelating Agents
  • Enzyme Inhibitors
  • Fluorescent Dyes
  • PLA2R1 protein, human
  • Receptors, Cell Surface
  • Receptors, Phospholipase A2
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Phospholipases A
  • Group IB Phospholipases A2
  • Group II Phospholipases A2
  • PLA2G1B protein, human
  • Leukocyte Elastase
  • Calcium