Cytosolic phospholipase A2 activation is essential for beta 1 and beta 2 integrin-dependent adhesion of human eosinophils

J Immunol. 1999 Sep 15;163(6):3423-9.

Abstract

We examined the role of cytosolic phospholipase A2 (cPLA2) during human eosinophil adherence to ICAM-1- or VCAM-1-coated plates. IL-5-stimulated eosinophils adhered to ICAM-1 through the beta 2 integrin CD11b/CD18, while nonstimulated eosinophils did not. By contrast, nonstimulated eosinophils adhered to VCAM-1 through the beta 1-integrin VLA-4/CD29. Both IL-5-induced adhesion to ICAM-1 and spontaneous adhesion to VCAM-1 corresponded temporally to cPLA2 phosphorylation, which accompanied enhanced catalytic activity of cPLA2. The structurally unrelated cPLA2 inhibitors, arachidonyl trifluoromethylketone and surfactin, significantly inhibited eosinophil adhesion to ICAM-1 and VCAM-1 in a concentration-dependent manner. Inhibition of secretory PLA2, 5-lipoxygenase, or cyclooxygenase did not affect eosinophil adhesion. Addition of arachidonic acid to eosinophils after cPLA2 inhibition with arachidonyl trifluoromethylketone or surfactin did not reverse the blockade of adhesion to ICAM-1 or VCAM-1. However, CV-6209, a receptor-specific antagonist of platelet-activating factor, inhibited all integrin-mediated adhesion. The activated conformation of CD11b as identified by the mAb, CBRM1/5, as well as quantitative surface CD11b expression were up-regulated after IL-5 stimulation. However, cPLA2 inhibition neither prevented CBRM1/5 expression nor blocked surface Mac-1 up-regulation caused by IL-5. Our data suggest that cPLA2 activation and its catalytic product platelet-activating factor play an essential role in regulating beta 1 and beta 2 integrin-dependent adhesion of eosinophils. This blockade occurs even in the presence of up-regulated eosinophil surface integrin.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arachidonic Acids / pharmacology
  • Bacterial Proteins / pharmacology
  • CD18 Antigens / physiology*
  • Cell Adhesion / immunology
  • Cell Survival / drug effects
  • Cytosol / enzymology*
  • Enzyme Activation / immunology
  • Enzyme Inhibitors / pharmacology
  • Eosinophils / drug effects
  • Eosinophils / enzymology*
  • Eosinophils / immunology
  • Eosinophils / physiology*
  • Epitopes / biosynthesis
  • Epitopes / immunology
  • Humans
  • Integrin beta1 / physiology*
  • Intercellular Adhesion Molecule-1 / physiology
  • Interleukin-5 / pharmacology
  • Lipopeptides
  • Macrophage-1 Antigen / biosynthesis
  • Macrophage-1 Antigen / immunology
  • Peptides, Cyclic*
  • Phospholipases A / antagonists & inhibitors
  • Phospholipases A / metabolism*
  • Phospholipases A2
  • Phosphorylation
  • Up-Regulation / drug effects
  • Up-Regulation / immunology
  • Vascular Cell Adhesion Molecule-1 / physiology

Substances

  • Arachidonic Acids
  • Bacterial Proteins
  • CD18 Antigens
  • Enzyme Inhibitors
  • Epitopes
  • Integrin beta1
  • Interleukin-5
  • Lipopeptides
  • Macrophage-1 Antigen
  • Peptides, Cyclic
  • Vascular Cell Adhesion Molecule-1
  • arachidonyltrifluoromethane
  • Intercellular Adhesion Molecule-1
  • surfactin peptide
  • Phospholipases A
  • Phospholipases A2