PMID- 30868053
OWN - NLM
STAT- MEDLINE
DCOM- 20200204
LR  - 20200309
IS  - 2211-5463 (Print)
IS  - 2211-5463 (Electronic)
IS  - 2211-5463 (Linking)
VI  - 9
IP  - 3
DP  - 2019 Mar
TI  - Macrophages engulf apoptotic and primary necrotic thymocytes through similar 
      phosphatidylserine-dependent mechanisms.
PG  - 446-456
LID - 10.1002/2211-5463.12584 [doi]
AB  - One of the major roles of professional phagocytes is the removal of dead cells in 
      the body. We know less about the clearance of necrotic cells than apoptotic cell 
      phagocytosis, despite the fact that both types of dead cells need to be cleared 
      together and necrotic cells appear often in pathological settings. In the present 
      study, we examined phagocytosis of heat- or H(2)O(2)-killed necrotic and 
      apoptotic thymocytes by mouse bone marrow-derived macrophages (BMDMs) in vitro 
      and found that the two cell types are engulfed at equal efficiency and compete 
      with each other when added together to BMDMs. Phagocytosis of both apoptotic and 
      necrotic thymocytes was decreased by (a) blocking phosphatidylserine on the 
      surface of dying cells; (b) inhibition of Mer tyrosine kinase, Tim-4, integrin beta3 
      receptor signaling, or Ras-related C3 botulinum toxin substrate 1 activity; or 
      (c) using BMDMs deficient for transglutaminase 2. Stimulation of liver X, 
      retinoid X, retinoic acid or glucocorticoid nuclear receptors in BMDMs enhanced 
      not only apoptotic, but also necrotic cell uptake. Electron microscopic analysis 
      of the engulfment process revealed that the morphology of phagosomes and the 
      phagocytic cup formed during the uptake of dying thymocytes is similar for 
      apoptotic and necrotic cells. Our data indicate that apoptotic and necrotic cells 
      are cleared via the same mechanisms, and removal of necrotic cells in vivo can be 
      facilitated by molecules known to enhance the uptake of apoptotic cells.
FAU - Budai, Zsofia
AU  - Budai Z
AD  - Department of Biochemistry and Molecular Biology Faculty of Medicine University 
      of Debrecen Hungary.
FAU - Ujlaky-Nagy, Laszlo
AU  - Ujlaky-Nagy L
AD  - Department of Biophysics and Cell Biology Faculty of Medicine University of 
      Debrecen Hungary.
FAU - Kis, Greta Nikoletta
AU  - Kis GN
AD  - Department of Anatomy, Histology and Embryology Faculty of Medicine University of 
      Debrecen Hungary.
FAU - Antal, Miklos
AU  - Antal M
AD  - Department of Anatomy, Histology and Embryology Faculty of Medicine University of 
      Debrecen Hungary.
FAU - Banko, Csaba
AU  - Banko C
AD  - Department of Biophysics and Cell Biology Faculty of Medicine University of 
      Debrecen Hungary.
FAU - Bacso, Zsolt
AU  - Bacso Z
AD  - Department of Biophysics and Cell Biology Faculty of Medicine and Faculty of 
      Pharmacy University of Debrecen Hungary.
FAU - Szondy, Zsuzsa
AU  - Szondy Z
AD  - Department of Biochemistry and Molecular Biology Faculty of Medicine University 
      of Debrecen Hungary.
AD  - Department of Basic Medical Sciences Faculty of Dentistry University of Debrecen 
      Hungary.
FAU - Sarang, Zsolt
AU  - Sarang Z
AD  - Department of Biochemistry and Molecular Biology Faculty of Medicine University 
      of Debrecen Hungary.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190213
PL  - England
TA  - FEBS Open Bio
JT  - FEBS open bio
JID - 101580716
RN  - 0 (Phosphatidylserines)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Animals
MH  - *Apoptosis/drug effects
MH  - Cells, Cultured
MH  - Hot Temperature
MH  - Hydrogen Peroxide/pharmacology
MH  - Macrophages/drug effects/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Necrosis/*metabolism
MH  - Phosphatidylserines/antagonists & inhibitors/*metabolism
MH  - Thymocytes/drug effects/*metabolism
PMC - PMC6396166
OTO - NOTNLM
OT  - apoptosis
OT  - macrophages
OT  - phagocytosis
OT  - phosphatidylserine
OT  - primary necrosis
COIS- The authors declare no conflict of interest.
EDAT- 2019/03/15 06:00
MHDA- 2019/03/15 06:01
PMCR- 2019/02/13
CRDT- 2019/03/15 06:00
PHST- 2018/08/06 00:00 [received]
PHST- 2018/11/22 00:00 [revised]
PHST- 2018/12/12 00:00 [accepted]
PHST- 2019/03/15 06:00 [entrez]
PHST- 2019/03/15 06:00 [pubmed]
PHST- 2019/03/15 06:01 [medline]
PHST- 2019/02/13 00:00 [pmc-release]
AID - FEB412584 [pii]
AID - 10.1002/2211-5463.12584 [doi]
PST - epublish
SO  - FEBS Open Bio. 2019 Feb 13;9(3):446-456. doi: 10.1002/2211-5463.12584. 
      eCollection 2019 Mar.