PMID- 33397789
OWN - NLM
STAT- Publisher
LR  - 20240222
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
DP  - 2021 Jan 4
TI  - Complement receptor 3 mediates both sinking phagocytosis and phagocytic cup 
      formation via distinct mechanisms.
LID - jbc.RA120.015346 [pii]
LID - 10.1074/jbc.RA120.015346 [doi]
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 knockout 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 FcgRs, 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  - Published under license by The American Society for Biochemistry and Molecular 
      Biology, Inc.
FAU - Walbaum, Stefan
AU  - Walbaum S
AD  - Institut fur Molekulare Zellbiologie, Germany.
FAU - Ambrosy, Benjamin
AU  - Ambrosy B
AD  - Institut fur Molekulare Zellbiologie, Germany.
FAU - Schutz, Paula
AU  - Schutz P
AD  - Institut fur Molekulare Zellbiologie, Germany.
FAU - Bachg, Anne C
AU  - Bachg AC
AD  - Institut fur Molekulare Zellbiologie.
FAU - Horsthemke, Markus
AU  - Horsthemke M
AD  - Institut fur Molekulare Zellbiologie, Germany.
FAU - Leusen, Jeanette H W
AU  - Leusen JHW
AD  - University Medical Center Utrecht, Netherlands.
FAU - Mocsai, Attila
AU  - Mocsai A
AUID- ORCID: 0000-0002-0512-1157
AD  - Semmelweis University School of Medicine, Hungary.
FAU - Hanley, Peter J
AU  - Hanley PJ
AD  - Institut fur Molekulare Zellbiologie, Germany.
LA  - eng
PT  - Journal Article
DEP - 20210104
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
SB  - IM
OTO - NOTNLM
OT  - complement
OT  - gene knockout
OT  - macrophage
OT  - microscopic imaging
OT  - phagocytosis
EDAT- 2021/01/06 06:00
MHDA- 2021/01/06 06:00
CRDT- 2021/01/05 06:15
PHST- 2021/01/04 00:00 [accepted]
PHST- 2020/07/22 00:00 [received]
PHST- 2021/01/05 06:15 [entrez]
PHST- 2021/01/06 06:00 [pubmed]
PHST- 2021/01/06 06:00 [medline]
AID - RA120.015346 [pii]
AID - 10.1074/jbc.RA120.015346 [doi]
PST - aheadofprint
SO  - J Biol Chem. 2021 Jan 4:jbc.RA120.015346. doi: 10.1074/jbc.RA120.015346.