The major characteristics of human atherosclerotic lesions are similar to those of a chronic inflammatory reaction, namely fibrosis, mesenchymal cell proliferation, the presence of resident macrophages, and cell necrosis. Atherosclerosis exhibits in addition the feature of lipid (mainly cholesterol) accumulation. The results of the present report demonstrate that a specific cholesterol-containing lipid particle present in human atherosclerotic lesions activates the complement system to completion. Thus, lipid could represent a stimulatory factor for the inflammatory reaction, whose underlying mechanistic basis may be, at least in part, complement activation. The complement-activating lipid was purified from saline extracts of aortic atherosclerotic lesions by sucrose density gradient centrifugation followed by molecular sieve chromatography on Sepharose 2B. It contained little protein other than albumin, was 100-500 nm in size, exhibited an unesterified to total cholesterol ratio of 0.58 and an unesterified cholesterol to phospholipid ratio of 1.2. The lipid, termed lesion lipid complement (LCA), activated the alternative pathway of complement in a dose-dependent manner. Lesion-extracted low density lipoprotein (LDL) obtained during the purification procedure failed to activate complement. Specific generation of C3a desArg and C5b-9 by LCA indicated C3/C5 convertase formation with activation proceeding to completion. Biochemical and electron microscopic evaluations revealed that much of the C5b-9 present in atherosclerotic lesions is membraneous, rather than fluid phase SC5b-9. The observations reported herein establish a link between lipid insudation and inflammation in atherosclerotic lesions via the mechanism of complement activation.
Skip Nav Destination
Article navigation
1 August 1990
Article|
August 01 1990
Isolation and characterization of a complement-activating lipid extracted from human atherosclerotic lesions.
P S Seifert,
P S Seifert
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
Search for other works by this author on:
F Hugo,
F Hugo
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
Search for other works by this author on:
J Tranum-Jensen,
J Tranum-Jensen
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
Search for other works by this author on:
U Zâhringer,
U Zâhringer
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
Search for other works by this author on:
M Muhly,
M Muhly
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
Search for other works by this author on:
S Bhakdi
S Bhakdi
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
Search for other works by this author on:
P S Seifert
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
F Hugo
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
J Tranum-Jensen
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
U Zâhringer
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
M Muhly
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
S Bhakdi
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1990) 172 (2): 547–557.
Citation
P S Seifert, F Hugo, J Tranum-Jensen, U Zâhringer, M Muhly, S Bhakdi; Isolation and characterization of a complement-activating lipid extracted from human atherosclerotic lesions.. J Exp Med 1 August 1990; 172 (2): 547–557. doi: https://doi.org/10.1084/jem.172.2.547
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement