PMID- 33839682
OWN - NLM
STAT- MEDLINE
DCOM- 20210818
LR  - 20210818
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 296
DP  - 2021 Jan-Jun
TI  - Complement receptor 3 mediates both sinking phagocytosis and phagocytic cup 
      formation via distinct mechanisms.
PG  - 100256
LID - S0021-9258(21)00023-5 [pii]
LID - 10.1016/j.jbc.2021.100256 [doi]
LID - 100256
AB  - A long-standing hypothesis is that complement receptors (CRs), especially CR3, 
      mediate sinking phagocytosis, but evidence is lacking. Alternatively, CRs have 
      been reported to induce membrane ruffles or phagocytic cups, akin to those 
      induced by Fcgamma receptors (FcgammaRs), but the details of these events are unclear. 
      Here we used real-time 3D imaging and KO mouse models to clarify how particles 
      (human red blood cells) are internalized by resident peritoneal F4/80(+) cells 
      (macrophages) via CRs and/or FcgammaRs. We first show that FcgammaRs mediate highly 
      efficient, rapid (2-3 min) phagocytic cup formation, which is completely 
      abolished by deletion or mutation of the FcR gamma chain or conditional deletion of 
      the signal transducer Syk. FcgammaR-mediated phagocytic cups robustly arise from any 
      point of cell-particle contact, including filopodia. In the absence of CR3, 
      FcgammaR-mediated phagocytic cups exhibit delayed closure and become aberrantly 
      elongated. Independent of FcgammaRs, CR3 mediates sporadic ingestion of 
      complement-opsonized particles by rapid phagocytic cup-like structures, typically 
      emanating from membrane ruffles and largely prevented by deletion of the 
      immunoreceptor tyrosine-based activation motif (ITAM) adaptors FcR gamma chain and 
      DAP12 or Syk. Deletion of ITAM adaptors or Syk clearly revealed that there is a 
      slow (10-25 min) sinking mode of phagocytosis via a restricted orifice. In 
      summary, we show that (1) CR3 indeed mediates a slow sinking mode of 
      phagocytosis, which is accentuated by deletion of ITAM adaptors or Syk, (2) CR3 
      induces phagocytic cup-like structures, driven by ITAM adaptors and Syk, and (3) 
      CR3 is involved in forming and closing FcgammaR-mediated phagocytic cups.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Walbaum, Stefan
AU  - Walbaum S
AD  - Institut fur Molekulare Zellbiologie, Westfalische Wilhems-Universitat Munster, 
      Munster, Germany.
FAU - Ambrosy, Benjamin
AU  - Ambrosy B
AD  - Institut fur Molekulare Zellbiologie, Westfalische Wilhems-Universitat Munster, 
      Munster, Germany.
FAU - Schutz, Paula
AU  - Schutz P
AD  - Institut fur Molekulare Zellbiologie, Westfalische Wilhems-Universitat Munster, 
      Munster, Germany.
FAU - Bachg, Anne C
AU  - Bachg AC
AD  - Institut fur Molekulare Zellbiologie, Westfalische Wilhems-Universitat Munster, 
      Munster, Germany.
FAU - Horsthemke, Markus
AU  - Horsthemke M
AD  - Institut fur Molekulare Zellbiologie, Westfalische Wilhems-Universitat Munster, 
      Munster, Germany.
FAU - Leusen, Jeanette H W
AU  - Leusen JHW
AD  - Center for Translational Immunology, University Medical Center Utrecht, Utrecht, 
      The Netherlands.
FAU - Mocsai, Attila
AU  - Mocsai A
AD  - Department of Physiology, Semmelweis University School of Medicine, Budapest, 
      Hungary.
FAU - Hanley, Peter J
AU  - Hanley PJ
AD  - Institut fur Molekulare Zellbiologie, Westfalische Wilhems-Universitat Munster, 
      Munster, Germany; Department of Physiology, Pathophysiology and Toxicology and 
      ZBAF (Centre for Biomedical Education and Research), Faculty of Health, School of 
      Medicine, Witten/Herdecke University, Witten, Germany. Electronic address: 
      peter.hanley@uni-wh.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210108
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Macrophage-1 Antigen)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
SB  - IM
MH  - Animals
MH  - Cell Membrane/*metabolism
MH  - Cells, Cultured
MH  - Humans
MH  - Immunoreceptor Tyrosine-Based Activation Motif
MH  - Macrophage-1 Antigen/*metabolism
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Phagocytosis
MH  - Pseudopodia/*metabolism
MH  - Signal Transduction
MH  - Syk Kinase/*metabolism
PMC - PMC7948798
OTO - NOTNLM
OT  - Complement system
OT  - knockout mice
OT  - live-cell imaging
OT  - macrophages
OT  - phagocytosis
COIS- Conflict of interest The authors declare that they have no conflicts of interest 
      with the contents of this article.
EDAT- 2021/04/12 06:00
MHDA- 2021/08/19 06:00
PMCR- 2021/01/08
CRDT- 2021/04/11 20:48
PHST- 2020/07/22 00:00 [received]
PHST- 2020/12/23 00:00 [revised]
PHST- 2021/01/04 00:00 [accepted]
PHST- 2021/04/12 06:00 [pubmed]
PHST- 2021/08/19 06:00 [medline]
PHST- 2021/04/11 20:48 [entrez]
PHST- 2021/01/08 00:00 [pmc-release]
AID - S0021-9258(21)00023-5 [pii]
AID - 100256 [pii]
AID - 10.1016/j.jbc.2021.100256 [doi]
PST - ppublish
SO  - J Biol Chem. 2021 Jan-Jun;296:100256. doi: 10.1016/j.jbc.2021.100256. Epub 2021 
      Jan 8.