Enhanced fMLP-stimulated chemotaxis in human neutrophils from individuals carrying the G protein beta3 subunit 825 T-allele.
We have recently described a C825T polymorphism in the gene encoding for the Gbeta3 subunit of heterotrimeric G proteins. The 825T allele is associated with a novel splice variant (Gbeta3-s) and enhanced signal transduction via pertussis toxin (PTX)-sensitive G proteins. fMLP-induced chemotaxis, but not O2- generation, was increased in neutrophils with the TC/TT (EC50 = 1.5 +/- 1.3 nM) genotypes compared to the CC genotype (EC50 = 5.9 +/- 1.5 nM). Maximal fMLP-induced increase in [Ca2+]i was significantly reduced in neutrophils from individuals with TC/TT genotype vs. CC genotype (212.9 +/- 10.1 nM vs. 146.4 +/- 24.2 nM). Gbeta3-s appears to be associated with enhanced immune cell function in humans.
Virchow
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S
Institut für Pharmakologie, Universitätsklinikum Essen, Germany. sebastian.virchow@uni-essen.de
Ansorge
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N
Rübben
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H
Siffert
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Siffert
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W
D000483:Alleles; D002118:Calcium / Q000097:blood; D002634:Chemotaxis, Leukocyte / Q000235:genetics* / Q000502:physiology; D019204:GTP-Binding Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000097:blood
D012333:RNA, Messenger; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019204:GTP-Binding Proteins; D002118:Calcium