TY - JOUR
T1 - Pentraxins PTX3 and CRP recruit C1q to cholesterol crystals and co-localize with the terminal complement complex in human atherosclerotic plaques
AU - Pilely, Katrine
AU - Fumagalli, Stefano
AU - Rosbjerg, Anne
AU - Skjoedt, Mikkel-Ole
AU - Perego, Carlo
AU - Ferrante, Angela Maria Rosaria
AU - De Simoni, Maria-Grazia
AU - Garred, Peter
PY - 2017
Y1 - 2017
N2 - Background: The pentraxins PTX3 and C-reactive protein (CRP)
are acute-phase proteins associated with increased risk of cardiovascular
events and are known to interact with the complement
system. Cholesterol crystals (CC) are found in atherosclerotic
plaques, where inflammation is a part of the initial process leading
to atherosclerosis. CC induce complement activation but the role of
the pentraxins PTX3, CRP and serum amyloid P component (SAP)
in CC mediated inflammation remains unknown.
Materials and methods: Binding and interaction of recombinant
and native PTX3, CRP or SAP with the complement pattern
recognition molecule C1q on CC was investigated in vitro by flow
cytometry and fluorescence microscopy. The role of C1q in phagocytosis
of CC was investigated by flow cytometry using hirudin
whole blood. Furthermore, co-localization of PTX3, CRP, and SAP
with complement activation product C5b-9 was investigated in vivo
inhumanatherosclerotic plaques by immunofluorescence and confocal
microscopy.
Results and conclusions: In the present study we report a
novel link between the presence of pentraxins in atherosclerotic
lesions and the known complement activation and inflammatory
response induced by CC. Recombinant and native PTX3, CRP and
SAP bound to CC in a concentration dependent manner. PTX3 and
CRP interacted with the complement pattern recognition molecule
C1q on CC by increasing the binding of both purified C1q and C1q
in plasma. Furthermore, CRP binding to CC increased C1q mediate complement activation and deposition of C5b-9. In a phagocytic
assay using whole blood we showed that phagocytosis of CC is
complement dependent and initiated by C1q mediated activation.
The pathophysiological relevance of the in vitro observations was
examined in vivo in human atherosclerotic plaques. PTX3, CRP, and
SAP were found in atherosclerotic plaques and were located mainly
in the cholesterol-rich necrotic core where they show partial colocalization
with complement activation product C5b-9.
In conclusion, this study identifies interaction between PTX3 or
CRP and C1q on CC as a new mechanism in the CC induced inflammation,
which may be highly important in the pathophysiology of
atherosclerosis.
AB - Background: The pentraxins PTX3 and C-reactive protein (CRP)
are acute-phase proteins associated with increased risk of cardiovascular
events and are known to interact with the complement
system. Cholesterol crystals (CC) are found in atherosclerotic
plaques, where inflammation is a part of the initial process leading
to atherosclerosis. CC induce complement activation but the role of
the pentraxins PTX3, CRP and serum amyloid P component (SAP)
in CC mediated inflammation remains unknown.
Materials and methods: Binding and interaction of recombinant
and native PTX3, CRP or SAP with the complement pattern
recognition molecule C1q on CC was investigated in vitro by flow
cytometry and fluorescence microscopy. The role of C1q in phagocytosis
of CC was investigated by flow cytometry using hirudin
whole blood. Furthermore, co-localization of PTX3, CRP, and SAP
with complement activation product C5b-9 was investigated in vivo
inhumanatherosclerotic plaques by immunofluorescence and confocal
microscopy.
Results and conclusions: In the present study we report a
novel link between the presence of pentraxins in atherosclerotic
lesions and the known complement activation and inflammatory
response induced by CC. Recombinant and native PTX3, CRP and
SAP bound to CC in a concentration dependent manner. PTX3 and
CRP interacted with the complement pattern recognition molecule
C1q on CC by increasing the binding of both purified C1q and C1q
in plasma. Furthermore, CRP binding to CC increased C1q mediate complement activation and deposition of C5b-9. In a phagocytic
assay using whole blood we showed that phagocytosis of CC is
complement dependent and initiated by C1q mediated activation.
The pathophysiological relevance of the in vitro observations was
examined in vivo in human atherosclerotic plaques. PTX3, CRP, and
SAP were found in atherosclerotic plaques and were located mainly
in the cholesterol-rich necrotic core where they show partial colocalization
with complement activation product C5b-9.
In conclusion, this study identifies interaction between PTX3 or
CRP and C1q on CC as a new mechanism in the CC induced inflammation,
which may be highly important in the pathophysiology of
atherosclerosis.
KW - Atherosclerosis
KW - C-reactive protein
KW - C1q
KW - C3
KW - Cholesterol crystals
KW - Complement activation
KW - Immunology
KW - Immunology and Allergy
KW - Membrane attack complex
KW - Pentraxin 3
KW - Serum amyloid P component
KW - Atherosclerosis
KW - C-reactive protein
KW - C1q
KW - C3
KW - Cholesterol crystals
KW - Complement activation
KW - Immunology
KW - Immunology and Allergy
KW - Membrane attack complex
KW - Pentraxin 3
KW - Serum amyloid P component
UR - http://hdl.handle.net/10807/119475
U2 - 10.1016/j.molimm.2017.06.241
DO - 10.1016/j.molimm.2017.06.241
M3 - Meeting Abstract
SN - 0161-5890
VL - 89
SP - 126
EP - 127
JO - Molecular Immunology
JF - Molecular Immunology
ER -