Serum amyloid P colocalizes with apolipoproteins in human atheroma: functional implications.
Serum amyloid P (SAP) is a common component of human amyloid deposits and has been identified in atherosclerotic lesions. We investigated the extent of the colocalization of SAP with apolipoprotein A-I (apoA-I), apoB, apoC-II, and apoE in human coronary arteries and explored potential roles for SAP in these regions, specifically the effect of SAP on the rate of formation and macrophage recognition of amyloid fibrils composed of apoC-II. Analysis of 42 human arterial sections by immunohistochemistry and double label fluorescence microscopy demonstrated that SAP and apoA-I, apoB, apoC-II, and apoE were increased significantly in atherosclerotic lesions compared with nonatherosclerotic segments. SAP colocalized with all four apolipoproteins to a similar extent, whereas plaque macrophages were found to correlate most strongly with apoC-II and apoB. In vitro studies showed that SAP accelerated the formation of amyloid fibrils by purified apoC-II. Furthermore, SAP strongly inhibited the phagocytosis of apoC-II amyloid fibrils by primary macrophages and macrophage cell lines and blocked the resultant production of reactive oxygen species. The ability of SAP to accelerate apoC-II amyloid fibril formation and inhibit macrophage recognition of apoC-II fibrils suggests that SAP may modulate the inflammatory response to amyloid fibrils in atherosclerosis.
Stewart
Cameron R
CR
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
Haw
Antonio
A
Lopez
Roland
R
McDonald
Thomas O
TO
Callaghan
Judy M
JM
McConville
Malcolm J
MJ
Moore
Kathryn J
KJ
Howlett
Geoffrey J
GJ
O'Brien
Kevin D
KD
D000818:Animals; D053304:Apolipoprotein C-II / Q000096:biosynthesis*; D001053:Apolipoproteins / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D017382:Reactive Oxygen Species / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000096:biosynthesis / Q000502:physiology*
D053304:Apolipoprotein C-II; D001053:Apolipoproteins; D017382:Reactive Oxygen Species; D000683:Serum Amyloid P-Component