PMID- 33070370
OWN - NLM
STAT- MEDLINE
DCOM- 20210830
LR  - 20220716
IS  - 1938-3673 (Electronic)
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 109
IP  - 6
DP  - 2021 Jun
TI  - Frontline Science: Extracellular CIRP generates a proinflammatory Ly6G(+) 
      CD11b(hi) subset of low-density neutrophils in sepsis.
PG  - 1019-1032
LID - 10.1002/JLB.3HI0620-416R [doi]
AB  - Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated 
      molecular pattern. Neutrophils present in the mononuclear cell fraction of Ficoll 
      gradient separation are called low-density neutrophils (LDNs). Here we report the 
      novel role of eCIRP on LDNs' heterogeneity in sepsis. Sepsis was induced in male 
      C57BL/6 wild-type (WT) and CIRP(-/-) mice by cecal ligation and puncture (CLP). 
      At 20 h after CLP, LDNs in the blood were isolated by Ficoll gradient separation, 
      followed by staining the cells with anti-Ly6G and anti-CD11b Abs and detection by 
      flow cytometry. Sepsis or recombinant murine CIRP (rmCIRP) injection in mice 
      resulted in significant increase in the frequency (%) and number of Ly6G(+) 
      CD11b(hi) and Ly6G(+) CD11b(lo) LDNs in the blood compared to sham- or 
      vehicle-treated mice. At 20 h of CLP, CIRP(-/-) mice had significantly lower 
      frequency and number of Ly6G(+) CD11b(hi) and Ly6G(+) CD11b(lo) LDNs in the blood 
      compared to WT mice. In sepsis mice or rmCIRP-injected mice, compared to Ly6G(+) 
      CD11b(lo) LDNs, the expression of CXCR4, ICAM-1, and iNOS and formation of 
      reactive oxygen species, and neutrophil extracellular traps in Ly6G(+) CD11b(hi) 
      LDNs in the blood were significantly increased. Treatment of WT bone 
      marrow-derived neutrophils (BMDNs) with rmCIRP increased Ly6G(+) CD11b(hi) LDN 
      frequency, whereas treatment of TLR4(-/-) BMDNs with rmCIRP significantly 
      decreased the frequency of Ly6G(+) CD11b(hi) LDNs. BMDNs' stimulation with rmCIRP 
      increased the expression of transcription factors in LDNs. eCIRP induces the 
      formation of a proinflammatory phenotype Ly6G(+) CD11b(hi) of LDNs through TLR4. 
      Targeting eCIRP may provide beneficial outcomes in sepsis by decreasing 
      proinflammatory Ly6G(+) CD11b(hi) LDNs.
CI  - (c)2020 Society for Leukocyte Biology.
FAU - Takizawa, Satoshi
AU  - Takizawa S
AD  - Center for Immunology and Inflammation, The Feinstein Institutes for Medical 
      Research, Manhasset, New York, USA.
FAU - Murao, Atsushi
AU  - Murao A
AD  - Center for Immunology and Inflammation, The Feinstein Institutes for Medical 
      Research, Manhasset, New York, USA.
FAU - Ochani, Mahendar
AU  - Ochani M
AD  - Center for Immunology and Inflammation, The Feinstein Institutes for Medical 
      Research, Manhasset, New York, USA.
FAU - Aziz, Monowar
AU  - Aziz M
AUID- ORCID: 0000-0002-8195-4505
AD  - Center for Immunology and Inflammation, The Feinstein Institutes for Medical 
      Research, Manhasset, New York, USA.
FAU - Wang, Ping
AU  - Wang P
AUID- ORCID: 0000-0002-1557-0394
AD  - Center for Immunology and Inflammation, The Feinstein Institutes for Medical 
      Research, Manhasset, New York, USA.
AD  - Department of Surgery, Donald and Barbara Zucker School of Medicine at 
      Hofstra/Northwell, Manhasset, New York, USA.
LA  - eng
GR  - R01 GM129633/GM/NIGMS NIH HHS/United States
GR  - R35 GM118337/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20201018
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Antigens, Ly)
RN  - 0 (Biomarkers)
RN  - 0 (CD11b Antigen)
RN  - 0 (Cirbp protein, mouse)
RN  - 0 (Ly6G antigen, mouse)
RN  - 0 (RNA-Binding Proteins)
SB  - IM
CIN - J Leukoc Biol. 2021 Jun;109(6):1013-1015. PMID: 33112444
MH  - Animals
MH  - Antigens, Ly/*metabolism
MH  - Biomarkers
MH  - CD11b Antigen/*metabolism
MH  - Disease Models, Animal
MH  - Disease Susceptibility
MH  - Extracellular Space/metabolism
MH  - Leukocyte Count
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Neutrophils/*metabolism
MH  - RNA-Binding Proteins/genetics/*metabolism
MH  - Sepsis/diagnosis/*etiology/*metabolism
PMC - PMC8053202
MID - NIHMS1636077
OTO - NOTNLM
OT  - CIRP
OT  - ICAM-1
OT  - NETs
OT  - low-density neutrophil
OT  - neutrophil
OT  - sepsis
COIS- Conflict of interest disclosure All authors declared that they have no competing 
      interests.
EDAT- 2020/10/19 06:00
MHDA- 2021/08/31 06:00
PMCR- 2022/06/01
CRDT- 2020/10/18 20:35
PHST- 2020/09/02 00:00 [revised]
PHST- 2020/06/29 00:00 [received]
PHST- 2020/10/03 00:00 [accepted]
PHST- 2020/10/19 06:00 [pubmed]
PHST- 2021/08/31 06:00 [medline]
PHST- 2020/10/18 20:35 [entrez]
PHST- 2022/06/01 00:00 [pmc-release]
AID - 10.1002/JLB.3HI0620-416R [doi]
PST - ppublish
SO  - J Leukoc Biol. 2021 Jun;109(6):1019-1032. doi: 10.1002/JLB.3HI0620-416R. Epub 
      2020 Oct 18.