PMID- 35779163
OWN - NLM
STAT- MEDLINE
DCOM- 20220823
LR  - 20240201
IS  - 1573-9546 (Electronic)
IS  - 1573-9538 (Print)
IS  - 1573-9538 (Linking)
VI  - 18
IP  - 3
DP  - 2022 Sep
TI  - Lysophosphatidylcholine induces adenosine release from macrophages via 
      TRPM7-mediated mitochondrial activation.
PG  - 317-343
LID - 10.1007/s11302-022-09878-y [doi]
AB  - Even though macrophages have the potential to harm tissues through excessive 
      release of inflammatory mediators, they play protective roles to maintain tissue 
      integrity. In this study, we hypothesized that lysophosphatidylcholine (LPC), via 
      G2A and A(2B) receptors, puts brakes on macrophages by the induction of adenosine 
      release which could contribute to termination of inflammation. Mechanistically, 
      LPC-induced PGE(2) production followed by the activation of cAMP/protein kinase A 
      (PKA) pathway which results in the activation of LKB1/AMPK signaling pathway 
      leading to increasing Mg(2+) influx concomitantly with an increase in 
      mitochondrial membrane potential (MMP, Deltapsi(m)) and ATP production. Then, ATP is 
      converted to adenosine intracellularly followed by efflux via ENT1. In a parallel 
      pathway, LPC-induced elevation of cytosolic calcium was essential for adenosine 
      release, and Ca(2+)/calmodulin signaling cooperated with PKA to regulate ENT1 
      permeation to adenosine. Pharmacological blockade of TRPM7 and antisense 
      treatment suppressed LPC-induced adenosine release and magnesium influx in bone 
      marrow-derived macrophages (BMDMs). Moreover, LPC suppressed LPS-induced 
      phosphorylation of connexin-43, which may counteract TLR4-mediated inflammatory 
      response. Intriguingly, we found LPC increased netrin-1 production from BMDMs. 
      Netrin-1 induces anti-inflammatory signaling via A(2B) receptor. In the presence 
      of adenosine deaminase which removes adenosine in the medium, the chemotaxis of 
      macrophages toward LPC was significantly increased. Hypoxia and metabolic 
      acidosis are usually developed in a variety of inflammatory situations such as 
      sepsis. We found LPC augmented hypoxia- or acidosis-induced adenosine release 
      from BMDMs. These results provide evidence of LPC-induced brake-like action on 
      macrophages by adenosine release via cellular magnesium signaling.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Nature B.V.
FAU - Youssef, Ahmed M
AU  - Youssef AM
AD  - Department of Pharmacology, College of Medicine, Hallym University, Chuncheon, 
      Gangwon-do, 24252, Republic of Korea.
FAU - Song, Dong-Keun
AU  - Song DK
AD  - Department of Pharmacology, College of Medicine, Hallym University, Chuncheon, 
      Gangwon-do, 24252, Republic of Korea. dksong@hallym.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20220702
PL  - Netherlands
TA  - Purinergic Signal
JT  - Purinergic signalling
JID - 101250499
RN  - 0 (Lysophosphatidylcholines)
RN  - 0 (TRPM Cation Channels)
RN  - 158651-98-0 (Netrin-1)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - I38ZP9992A (Magnesium)
RN  - K72T3FS567 (Adenosine)
SB  - IM
RIN - Purinergic Signal. 2023 Dec;19(4):709. PMID: 37572178
MH  - *Adenosine/metabolism
MH  - Adenosine Triphosphate
MH  - Cyclic AMP-Dependent Protein Kinases
MH  - Hypoxia
MH  - *Lysophosphatidylcholines/pharmacology
MH  - *Macrophages/metabolism
MH  - Magnesium
MH  - Netrin-1
MH  - Protein Serine-Threonine Kinases
MH  - *TRPM Cation Channels
PMC - PMC9391566
OTO - NOTNLM
OT  - Adenosine release
OT  - Bone marrow-derived macrophages
OT  - Intracellular magnesium
OT  - Lipopolysaccharide
OT  - Lysophosphatidylcholine
OT  - TRPM7
COIS- The authors declare no competing interests.
EDAT- 2022/07/03 06:00
MHDA- 2022/08/24 06:00
PMCR- 2023/01/02
CRDT- 2022/07/02 11:16
PHST- 2022/01/14 00:00 [received]
PHST- 2022/06/13 00:00 [accepted]
PHST- 2022/07/03 06:00 [pubmed]
PHST- 2022/08/24 06:00 [medline]
PHST- 2022/07/02 11:16 [entrez]
PHST- 2023/01/02 00:00 [pmc-release]
AID - 10.1007/s11302-022-09878-y [pii]
AID - 9878 [pii]
AID - 10.1007/s11302-022-09878-y [doi]
PST - ppublish
SO  - Purinergic Signal. 2022 Sep;18(3):317-343. doi: 10.1007/s11302-022-09878-y. Epub 
      2022 Jul 2.