Different G(i)-coupled chemoattractant receptors signal qualitatively different functions in human neutrophils.
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.
Berger
Miles
M
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 650 W 168th Street, New York, NY 10027, USA.
Budhu
Sadna
S
Lu
Emily
E
Li
Yongmei
Y
Loike
Devora
D
Silverstein
Samuel C
SC
Loike
John D
JD
D018821:CD18 Antigens / Q000502:physiology; D002448:Cell Adhesion; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D037342:Pertussis Toxin; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018821:CD18 Antigens; D002630:Chemotactic Factors; D016326:Extracellular Matrix Proteins; D011971:Receptors, Immunologic; D010566:Virulence Factors, Bordetella; D006861:Hydrogen Peroxide; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins