PMID- 29692344
OWN - NLM
STAT- MEDLINE
DCOM- 20190308
LR  - 20190308
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 2
IP  - 8
DP  - 2018 Apr 24
TI  - Red pulp macrophages in the human spleen are a distinct cell population with a 
      unique expression of Fc-gamma receptors.
PG  - 941-953
LID - 10.1182/bloodadvances.2017015008 [doi]
AB  - Tissue-resident macrophages in the spleen play a major role in the clearance of 
      immunoglobulin G (IgG)-opsonized blood cells, as occurs in immune 
      thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Blood cells are 
      phagocytosed via the Fc-gamma receptors (FcgammaRs), but little is known about the FcgammaR 
      expression on splenic red pulp macrophages in humans, with only a few previous 
      studies that showed conflicting results. We developed a novel method to 
      specifically isolate red pulp macrophages from 82 human spleens. Surface 
      expression of various receptors and phagocytic capacity was analyzed by flow 
      cytometry and immunofluorescence of tissue sections. Red pulp macrophages were 
      distinct from splenic monocytes and blood monocyte-derived macrophages on various 
      surface markers. Human red pulp macrophages predominantly expressed the 
      low-affinity receptors FcgammaRIIa and FcgammaRIIIa. In contrast to blood 
      monocyte-derived macrophages, red pulp macrophages did not express the inhibitory 
      FcgammaRIIb. Red pulp macrophages expressed very low levels of the high-affinity 
      receptor FcgammaRI. Messenger RNA transcript analysis confirmed this expression 
      pattern. Unexpectedly and despite these differences in FcgammaR expression, 
      phagocytosis of IgG-opsonized blood cells by red pulp macrophages was dependent 
      on the same FcgammaRs as phagocytosis by blood monocyte-derived macrophages, 
      especially in regarding the response to IV immunoglobulin. Concluding, we show 
      the distinct nature of splenic red pulp macrophages in human subjects. Knowledge 
      on the FcgammaR expression and usage of these cells is important for understanding 
      and improving treatment strategies for autoimmune diseases such as ITP and AIHA.
CI  - (c) 2018 by The American Society of Hematology.
FAU - Nagelkerke, Sietse Q
AU  - Nagelkerke SQ
AD  - Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands.
AD  - Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 
      Amsterdam, The Netherlands.
FAU - Bruggeman, Christine W
AU  - Bruggeman CW
AD  - Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands.
AD  - Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 
      Amsterdam, The Netherlands.
FAU - den Haan, Joke M M
AU  - den Haan JMM
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical 
      Center, Amsterdam, The Netherlands.
FAU - Mul, Erik P J
AU  - Mul EPJ
AD  - Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 
      Amsterdam, The Netherlands.
AD  - Department of Central Facility Research, Sanquin Research, Amsterdam, The 
      Netherlands; and.
FAU - van den Berg, Timo K
AU  - van den Berg TK
AD  - Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands.
AD  - Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 
      Amsterdam, The Netherlands.
FAU - van Bruggen, Robin
AU  - van Bruggen R
AD  - Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands.
AD  - Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 
      Amsterdam, The Netherlands.
FAU - Kuijpers, Taco W
AU  - Kuijpers TW
AD  - Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands.
AD  - Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 
      Amsterdam, The Netherlands.
AD  - Department of Pediatric Hematology, Immunology & Infectious Disease, Emma 
      Children's Hospital at the Academic Medical Center, University of Amsterdam, 
      Amsterdam, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (FCGR2A protein, human)
RN  - 0 (FCGR3A protein, human)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Humans
MH  - Macrophages/cytology/*metabolism
MH  - Phagocytosis/immunology
MH  - Receptors, IgG/analysis/immunology/*metabolism
MH  - Spleen/*cytology
PMC - PMC5916003
COIS- Conflict-of-interest disclosure: The authors declare no competing financial 
      interest.
EDAT- 2018/04/26 06:00
MHDA- 2019/03/09 06:00
PMCR- 2018/04/24
CRDT- 2018/04/26 06:00
PHST- 2017/12/06 00:00 [received]
PHST- 2018/03/06 00:00 [accepted]
PHST- 2018/04/26 06:00 [entrez]
PHST- 2018/04/26 06:00 [pubmed]
PHST- 2019/03/09 06:00 [medline]
PHST- 2018/04/24 00:00 [pmc-release]
AID - bloodadvances.2017015008 [pii]
AID - 2017/015008 [pii]
AID - 10.1182/bloodadvances.2017015008 [doi]
PST - ppublish
SO  - Blood Adv. 2018 Apr 24;2(8):941-953. doi: 10.1182/bloodadvances.2017015008.