PMID- 25352126
OWN - NLM
STAT- MEDLINE
DCOM- 20150220
LR  - 20221109
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 124
IP  - 25
DP  - 2014 Dec 11
TI  - Inhibition of FcgammaR-mediated phagocytosis by IVIg is independent of IgG-Fc 
      sialylation and FcgammaRIIb in human macrophages.
PG  - 3709-18
LID - 10.1182/blood-2014-05-576835 [doi]
AB  - In immune thrombocytopenia and warm autoimmune hemolytic anemia, circulating 
      immunoglobulin G (IgG)-opsonized blood cells are cleared from the circulation by 
      macrophages. Administration of intravenous immunoglobulin (IVIg) can prevent 
      uptake, but the exact working mechanism is not known. The prevailing theory from 
      murine studies, which states that Fc-sialylated IgG alters the balance between 
      activating and inhibitory Fc-gamma receptors (FcgammaRs) by inducing upregulation of 
      the inhibitory FcgammaRIIb on effector macrophages, is currently debated. We studied 
      phagocytosis of IgG-opsonized blood cells in a human system, assessing the effect 
      of IVIg and blocking anti-FcgammaR F(ab')2 fragments on uptake by monocyte-derived 
      macrophages (both M1 and M2 macrophages). Phagocytosis was remarkably sensitive 
      to administration of IVIg, but unexpectedly, recombinant Fc-sialylated IgG or 
      sialic acid-enriched IVIg were equally active as unsialylated IgG fractions in 
      mediating this inhibition, independent of FcgammaRIIb expression. Instead, IVIg 
      inhibited phagocytosis by direct blockade of FcgammaRs. IgG fractions enriched for 
      IgG dimers with enhanced avidity for FcgammaRs showed increased inhibition compared 
      with monomeric IgG fractions. Together, our data demonstrate that inhibition of 
      IgG-mediated phagocytosis in human macrophages by IVIg is dependent on the 
      capacity to directly bind FcgammaRs but is independent of FcgammaRIIb or sialylation of 
      the Fc fragment in the human setting.
CI  - (c) 2014 by The American Society of Hematology.
FAU - Nagelkerke, Sietse Q
AU  - Nagelkerke SQ
AD  - Department of Blood Cell Research.
FAU - Dekkers, Gillian
AU  - Dekkers G
AD  - Department of Experimental Immunohematology, and.
FAU - Kustiawan, Iwan
AU  - Kustiawan I
AD  - Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory, 
      Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
FAU - van de Bovenkamp, Fleur S
AU  - van de Bovenkamp FS
AD  - Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory, 
      Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
FAU - Geissler, Judy
AU  - Geissler J
AD  - Department of Blood Cell Research.
FAU - Plomp, Rosina
AU  - Plomp R
AD  - Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, 
      The Netherlands; and.
FAU - Wuhrer, Manfred
AU  - Wuhrer M
AD  - Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, 
      The Netherlands; and.
FAU - Vidarsson, Gestur
AU  - Vidarsson G
AD  - Department of Experimental Immunohematology, and.
FAU - Rispens, Theo
AU  - Rispens T
AD  - Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory, 
      Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
FAU - van den Berg, Timo K
AU  - van den Berg TK
AD  - Department of Blood Cell Research.
FAU - Kuijpers, Taco W
AU  - Kuijpers TW
AD  - Department of Blood Cell Research, Emma Children's Hospital, Academic Medical 
      Center, University of Amsterdam, Amsterdam, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141028
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (FCGR2B protein, human)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Receptors, IgG)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - GZP2782OP0 (N-Acetylneuraminic Acid)
SB  - IM
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Erythrocytes/immunology
MH  - Flow Cytometry
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/immunology/pharmacology
MH  - Humans
MH  - Immunoglobulin Fc Fragments/*immunology/metabolism
MH  - Immunoglobulin G/immunology
MH  - Immunoglobulins, Intravenous/*immunology/pharmacology
MH  - Macrophage Colony-Stimulating Factor/immunology/pharmacology
MH  - Macrophages/drug effects/*immunology/metabolism
MH  - N-Acetylneuraminic Acid/immunology/metabolism
MH  - Phagocytosis/drug effects/*immunology
MH  - Receptors, IgG/*immunology/metabolism
EDAT- 2014/10/30 06:00
MHDA- 2015/02/24 06:00
CRDT- 2014/10/30 06:00
PHST- 2014/10/30 06:00 [entrez]
PHST- 2014/10/30 06:00 [pubmed]
PHST- 2015/02/24 06:00 [medline]
AID - S0006-4971(20)39579-3 [pii]
AID - 10.1182/blood-2014-05-576835 [doi]
PST - ppublish
SO  - Blood. 2014 Dec 11;124(25):3709-18. doi: 10.1182/blood-2014-05-576835. Epub 2014 
      Oct 28.