PMID- 29929985
OWN - NLM
STAT- MEDLINE
DCOM- 20190215
LR  - 20210314
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 293
IP  - 33
DP  - 2018 Aug 17
TI  - Regulator of G protein signaling 5 restricts neutrophil chemotaxis and 
      trafficking.
PG  - 12690-12702
LID - S0021-9258(20)31324-7 [pii]
LID - 10.1074/jbc.RA118.002404 [doi]
AB  - 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.
FAU - Chan, Eunice C
AU  - Chan EC
AD  - Molecular Signal Transduction Section, NIAID, National Institutes of Health, 
      Bethesda, Maryland 20892.
FAU - Ren, Chunguang
AU  - Ren C
AD  - Department of Pharmacology, Yale University School of Medicine, New Haven, 
      Connecticut 06510.
FAU - Xie, Zhihui
AU  - Xie Z
AD  - Molecular Signal Transduction Section, NIAID, National Institutes of Health, 
      Bethesda, Maryland 20892.
FAU - Jude, Joseph
AU  - Jude J
AD  - Rutgers Institute for Translational Medicine and Science, Child Health Institute 
      of New Jersey, Rutgers New Jersey School of Medicine, Rutgers, New Jersey 07103.
FAU - Barker, Tolga
AU  - Barker T
AD  - Molecular Signal Transduction Section, NIAID, National Institutes of Health, 
      Bethesda, Maryland 20892.
FAU - Koziol-White, Cynthia A
AU  - Koziol-White CA
AD  - Rutgers Institute for Translational Medicine and Science, Child Health Institute 
      of New Jersey, Rutgers New Jersey School of Medicine, Rutgers, New Jersey 07103.
FAU - Ma, Michelle
AU  - Ma M
AD  - Inflammation Immunobiology Section, NIAID, National Institutes of Health, 
      Bethesda, Maryland 20892.
FAU - Panettieri, Reynold A Jr
AU  - Panettieri RA Jr
AD  - Rutgers Institute for Translational Medicine and Science, Child Health Institute 
      of New Jersey, Rutgers New Jersey School of Medicine, Rutgers, New Jersey 07103.
FAU - Wu, Dianqing
AU  - Wu D
AD  - Department of Pharmacology, Yale University School of Medicine, New Haven, 
      Connecticut 06510.
FAU - Rosenberg, Helene F
AU  - Rosenberg HF
AD  - Inflammation Immunobiology Section, NIAID, National Institutes of Health, 
      Bethesda, Maryland 20892.
FAU - Druey, Kirk M
AU  - Druey KM
AD  - Molecular Signal Transduction Section, NIAID, National Institutes of Health, 
      Bethesda, Maryland 20892. Electronic address: kdruey@niaid.nih.gov.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20180621
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chemotactic Factors)
RN  - 0 (RGS Proteins)
RN  - 0 (RGS5 protein, human)
RN  - 0 (Rgs5 protein, mouse)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
SB  - IM
MH  - Animals
MH  - Cell Adhesion
MH  - Cell Movement
MH  - Cells, Cultured
MH  - Chemotactic Factors/*metabolism
MH  - *Chemotaxis
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - N-Formylmethionine Leucyl-Phenylalanine/metabolism
MH  - Neutrophils/metabolism/*pathology
MH  - RGS Proteins/*metabolism/*physiology
MH  - Signal Transduction
PMC - PMC6102127
OTO - NOTNLM
OT  - G protein-coupled receptor
OT  - GPCR
OT  - RGS
OT  - chemotaxis
OT  - inflammation
OT  - innate immunity
OT  - leukocyte
OT  - neutrophil
OT  - regulator of G protein signaling
OT  - trafficking
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article
EDAT- 2018/06/23 06:00
MHDA- 2019/02/16 06:00
PMCR- 2019/08/17
CRDT- 2018/06/23 06:00
PHST- 2018/02/12 00:00 [received]
PHST- 2018/06/14 00:00 [revised]
PHST- 2018/06/23 06:00 [pubmed]
PHST- 2019/02/16 06:00 [medline]
PHST- 2018/06/23 06:00 [entrez]
PHST- 2019/08/17 00:00 [pmc-release]
AID - S0021-9258(20)31324-7 [pii]
AID - RA118.002404 [pii]
AID - 10.1074/jbc.RA118.002404 [doi]
PST - ppublish
SO  - J Biol Chem. 2018 Aug 17;293(33):12690-12702. doi: 10.1074/jbc.RA118.002404. Epub 
      2018 Jun 21.