Related Experiment Video
Updated: Jul 10, 2026

Imaging G Protein-coupled Receptor-mediated Chemotaxis and its Signaling Events in Neutrophil-like HL60 Cells
Published on: September 14, 2016
Small molecule disruption of G protein beta gamma subunit signaling inhibits neutrophil chemotaxis and inflammation
D M Lehmann1, A M P B Seneviratne, A V Smrcka
1University of Rochester, Department of Pharmacology and Physiology, 601 Elmwood Ave., Box 711, Rochester, NY 14642, USA.
Abstract:
G protein betagamma subunit-dependent signaling is important for chemoattractant-dependent leukocyte chemotaxis. Selective small molecule targeting of phosphoinositide 3-kinase (PI3-kinase) gamma catalytic activity is a target of interest for anti-inflammatory pharmaceutical development. In this study, we examined whether small-molecule inhibition of Gbetagamma-dependent signaling, including Gbetagamma-dependent activation of PI3-kinase gamma and Rac1, could inhibit chemoattractant-dependent neutrophil migration in vitro and inflammation in vivo. Small-molecule Gbetagamma inhibitors suppressed fMLP-stimulated Rac activation, superoxide production, and PI3-kinase activation in differentiated HL60 cells. These compounds also blocked fMLP-dependent chemotaxis in HL60 cells and primary human neutrophils. Systemic administration inhibited paw edema and neutrophil infiltration in a mouse carrageenan-induced paw edema model. Overall, the data demonstrate that targeting Gbetagamma-regulation may be an effective anti-inflammation strategy.
Related Concept Videos
Chemotaxis and Direction of Cell Migration
GPCR Desensitization
Activation and Inactivation of G Proteins
Amplifying Signals via Enzymatic Cascade
GPCRs Regulate Adenylyl Cylase Activity
Two...
Nitric Oxide Signaling Pathway

