Different Gi-coupled chemoattractant receptors signal qualitatively different functions in human neutrophils

Abstract

AbstractfMLP- or TNF-α-stimulated neutrophils produced H2O2 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 H2O2 when they adhered to any of these surfaces. fMLP and TNF-α were much more potent than LTB4 and IL-8 in stimulating neutrophils to up-regulate and to activate their αMβ2 integrins, as measured by the binding of specific monoclonal antibodies. Pretreatment of neutrophils with pertussis toxin completely blocked their production of H2O2 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 Gα 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 β and/or γ subunits or other factors by their cognate receptors.