Pertussis toxin inhibits human neutrophil responses mediated by the 42-kilodalton IgG Fc receptor.
The effects of pertussis toxin (PT) on human neutrophil responses mediated by the 42-kDa IgG Fc R (Fc gamma R42) were compared with its effects on responses mediated by the FMLP receptor. Pre-treatment of neutrophils with PT completely inhibited FMLP stimulation of superoxide production and blocked over 95% of FMLP-stimulated degranulation. PT inhibited superoxide production stimulated by Fc gamma R42 cross-linking by 92%. In contrast, degranulation stimulated by Fc gamma R42 was only partially inhibited, with beta-glucuronidase release inhibited by 54%, lysozyme by 33%, and lactoferrin by 78%. With either stimulus, PT inhibition was maximal in the range from 1.8 to 2 micrograms/ml. Responses to both stimuli declined in a parallel fashion with increasing time of exposure to PT with maximal inhibition occurring after 2 h of exposure. Inhibition of FMLP responses and Fc gamma R42-mediated superoxide production, but not degranulation, correlated with ADP-ribosylation of a 45-kDa membrane protein. Inhibition by PT of Fc gamma R42-mediated responses was not due to a change in receptor number. These data suggest that activation of polymorphonuclear neutrophils via Fc gamma R42 proceeds through two pathways, only one of which is regulated by a PT-sensitive G protein.
Feister
A J
AJ
Department of Medicine, Medical College of Virginia, Richmond 23298.
Browder
B
B
Willis
H E
HE
Mohanakumar
T
T
Ruddy
S
S
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D001667:Binding, Competitive; D003594:Cytoplasmic Granules / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D008970:Molecular Weight; D009113:Muramidase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D037342:Pertussis Toxin; D010587:Phagocytosis / Q000187:drug effects; D011961:Receptors, Fc / Q000187:drug effects* / Q000502:physiology; D017452:Receptors, IgG; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D009240:N-Formylmethionine Leucyl-Phenylalanine; D037342:Pertussis Toxin; D009113:Muramidase; D005966:Glucuronidase