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Differential binding of inorganic particles to MARCO
#MMPMID18836211
Thakur SA
; Hamilton R Jr
; Pikkarainen T
; Holian A
Toxicol Sci
2009[Jan]; 107
(1
): 238-46
PMID18836211
show ga
Alveolar macrophages (AM) in the lung have been documented to play pivotal roles
in inflammation and fibrosis (silicosis) following inhalation of crystalline
silica (CSiO(2)). In contrast, exposure to either titanium dioxide (TiO(2)) or
amorphous silica (ASiO(2)) is considered relatively benign. The scavenger
receptor macrophage receptor with collagenous structure (MARCO), expressed on AM,
binds and internalizes environmental particles such as silica and TiO(2). Only
CSiO(2) is toxic to AM, while ASiO(2) and TiO(2) are not. We hypothesize that
differences in induction of pathology between toxic CSiO(2) and nontoxic
particles ASiO(2) and TiO(2) may be related to their differential binding to
MARCO. In vitro studies with Chinese hamster ovary (CHO) cells transfected with
human MARCO and mutants were conducted to better characterize MARCO-particulate
(ASiO(2), CSiO(2), and TiO(2)) interactions. Results with MARCO-transfected CHO
cells and MARCO-specific antibody demonstrated that the scavenger receptor
cysteine-rich (SRCR) domain of MARCO was required for particle binding for all
the tested particles. Only TiO(2) required divalent cations (viz., Ca(+2) and/or
Mg(+2)) for binding to MARCO, and results from competitive binding studies
supported the notion that TiO(2) and both the silica particles bound to different
motifs in SRCR domain of MARCO. The results also suggest that particle shape
and/or crystal structure may be the determinants linking particle binding to
MARCO and cytotoxicity. Taken together, these results demonstrate that the SRCR
domain of MARCO is required for particle binding and that involvement of
different regions of SRCR domain may distinguish downstream events following
particle binding.
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