Cleavage of Type I Collagen by Fibroblast Activation Protein-? Enhances Class A
Scavenger Receptor Mediated Macrophage Adhesion
#MMPMID26934296
Mazur A
; Holthoff E
; Vadali S
; Kelly T
; Post SR
PLoS One
2016[]; 11
(3
): e0150287
PMID26934296
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Pathophysiological conditions such as fibrosis, inflammation, and tumor
progression are associated with modification of the extracellular matrix (ECM).
These modifications create ligands that differentially interact with cells to
promote responses that drive pathological processes. Within the tumor stroma,
fibroblasts are activated and increase the expression of type I collagen. In
addition, activated fibroblasts specifically express fibroblast activation
protein-? (FAP), a post-prolyl peptidase. Although FAP reportedly cleaves type I
collagen and contributes to tumor progression, the specific pathophysiologic role
of FAP is not clear. In this study, the possibility that FAP-mediated cleavage of
type I collagen modulates macrophage interaction with collagen was examined using
macrophage adhesion assays. Our results demonstrate that FAP selectively cleaves
type I collagen resulting in increased macrophage adhesion. Increased macrophage
adhesion to FAP-cleaved collagen was not affected by inhibiting integrin-mediated
interactions, but was abolished in macrophages lacking the class A scavenger
receptor (SR-A/CD204). Further, SR-A expressing macrophages localize with
activated fibroblasts in breast tumors of MMTV-PyMT mice. Together, these results
demonstrate that FAP-cleaved collagen is a substrate for SR-A-dependent
macrophage adhesion, and suggest that by modifying the ECM, FAP plays a novel
role in mediating communication between activated fibroblasts and macrophages.
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