Highlights
- •Alpha-cyclodextrin (ACD) inhibits deposition of complement activation products on cholesterol crystals.
- •ACD inhibits binding of C1q (via IgM) and ficolin-2 to cholesterol crystals.
- •ACD inhibits phagocytosis and production of ROS in granulocytes and monocytes.
- •ACD dissolves cholesterol crystals over time.
Abstract
Background and aims
Cholesterol crystal (CC)-induced inflammation is a critical step in the development
of atherosclerosis. CCs activate the complement system and induce an inflammatory
response resulting in phagocytosis of the CCs, production of reactive oxygen species
(ROS) and release of cytokines. The cyclodextrin 2-hydroxypropyl-β-cyclodextrin has
been found to reduce CC-induced complement activation and induce regression of established
atherosclerotic plaques in a mouse model of atherosclerosis, thus inhibition of complement
with cyclodextrins is a potential new strategy for treatment of inflammation during
atherosclerosis. We hypothesized that other cyclodextrins, like α-cyclodextrin, may
have related functions.
Methods
The effect of cyclodextrins on CC-induced complement activation, phagocytosis, and
production of ROS from granulocytes and monocytes was investigated by flow cytometry
and ELISA.
Results
We showed that α-cyclodextrin strongly inhibited CC-induced complement activation
by inhibiting binding of the pattern recognition molecules C1q (via IgM) and ficolin-2.
The reduced CC-induced complement activation mediated by α-cyclodextrin resulted in
reduced phagocytosis and reduced ROS production in monocytes and granulocytes. Alpha-cyclodextrin
was the most effective inhibitor of CC-induced complement activation, with the reduction
in deposition of complement activation products being significantly different from
the reduction induced by 2-hydroxypropyl-β-cyclodextrin. We also found that α-cyclodextrin
was able to dissolve CCs.
Conclusions
This study identified α-cyclodextrin as a potential candidate in the search for therapeutics
to prevent CC-induced inflammation in atherosclerosis.
Graphical abstract
Graphical Abstract
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Article info
Publication history
Published online: February 03, 2019
Accepted:
January 23,
2019
Received in revised form:
December 13,
2018
Received:
November 13,
2018
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
