Different G(i)-coupled chemoattractant receptors signal qualitatively different functions in human neutrophils

J Leukoc Biol. 2002 May;71(5):798-806.

Abstract

fMLP- or TNF-alpha-stimulated neutrophils produced H(2)O(2) when they adhered to fibrinogen-coated surfaces but not when they adhered to collagen I-, collagen IV-, or Matrigel-coated surfaces. In contrast, LTB4- or IL-8-stimulated neutrophils did not produce H(2)O(2) when they adhered to any of these surfaces. fMLP and TNF-alpha were much more potent than LTB4 and IL-8 in stimulating neutrophils to up-regulate and to activate their alpha(M)beta(2) integrins, as measured by the binding of specific monoclonal antibodies. Pretreatment of neutrophils with pertussis toxin completely blocked their production of H(2)O(2) on fibrinogen-coated surfaces in response to fMLP and their migration through Matrigel in response to fMLP, LTB4, and IL-8. These data show that although the fMLP, LTB4, and IL-8 receptors are coupled to pertussis toxin-sensitive Galpha proteins, they signal neutrophils to initiate qualitatively different effector functions. We propose that the qualitative differences in effector functions signaled by different chemoattractants reflect qualitative differences in using G-protein beta and/or gamma subunits or other factors by their cognate receptors.

Publication types

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

MeSH terms

  • CD18 Antigens / physiology
  • Cell Adhesion
  • Cells, Cultured
  • Chemotactic Factors / antagonists & inhibitors
  • Chemotactic Factors / pharmacology*
  • Chemotaxis, Leukocyte* / drug effects
  • Extracellular Matrix Proteins / pharmacology
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Kinetics
  • Neutrophils / drug effects
  • Neutrophils / immunology*
  • Pertussis Toxin
  • Receptors, Immunologic / metabolism*
  • Signal Transduction
  • Virulence Factors, Bordetella / pharmacology

Substances

  • CD18 Antigens
  • Chemotactic Factors
  • Extracellular Matrix Proteins
  • Receptors, Immunologic
  • Virulence Factors, Bordetella
  • Hydrogen Peroxide
  • Pertussis Toxin
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Heterotrimeric GTP-Binding Proteins