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J Biol Chem. 2018 Aug 17;293(33):12690-12702. doi: 10.1074/jbc.RA118.002404. Epub 2018 Jun 21.

Regulator of G protein signaling 5 restricts neutrophil chemotaxis and trafficking.

Author information

From the Molecular Signal Transduction Section.
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510, and.
Rutgers Institute for Translational Medicine and Science, Child Health Institute of New Jersey, Rutgers New Jersey School of Medicine, Rutgers, New Jersey 07103.
Inflammation Immunobiology Section, NIAID, National Institutes of Health, Bethesda, Maryland 20892.
From the Molecular Signal Transduction Section,


Neutrophils are white blood cells that are mobilized to damaged tissues and to sites of pathogen invasion, providing the first line of host defense. Chemokines displayed on the surface of blood vessels promote migration of neutrophils to these sites, and tissue- and pathogen-derived chemoattractant signals, including N-formylmethionylleucylphenylalanine (fMLP), elicit further migration to sites of infection. Although nearly all chemoattractant receptors use heterotrimeric G proteins to transmit signals, many of the mechanisms lying downstream of chemoattractant receptors that either promote or limit neutrophil motility are incompletely defined. Here, we show that regulator of G protein signaling 5 (RGS5), a protein that modulates G protein activity, is expressed in both human and murine neutrophils. We detected significantly more neutrophils in the airways of Rgs5-/- mice than WT counterparts following acute respiratory virus infection and in the peritoneum in response to injection of thioglycollate, a biochemical proinflammatory stimulus. RGS5-deficient neutrophils responded with increased chemotaxis elicited by the chemokines CXC motif chemokine ligand 1 (CXCL1), CXCL2, and CXCL12 but not fMLP. Moreover, adhesion of these cells was increased in the presence of both CXCL2 and fMLP. In summary, our results indicate that RGS5 deficiency increases chemotaxis and adhesion, leading to more efficient neutrophil mobilization to inflamed tissues in mice. These findings suggest that RGS5 expression and activity in neutrophils determine their migrational patterns in the complex microenvironments characteristic of inflamed tissues.


G protein–coupled receptor; GPCR; RGS; chemotaxis; inflammation; innate immunity; leukocyte; neutrophil; regulator of G protein signaling; trafficking

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