Complement receptors and regulatory proteins in human atherosclerotic lesions.

Abstract

Terminal complement complexes arise as a final product of the complement activation sequence, and their assembly from native C5 through C9 proteins involves neoantigen formation, i.e., creation of unique antigenic epitopes not present on the native unassembled proteins. 89 Thus, immunological detection techniques utilizing antibodies to C5b-9 neoantigens reliably indicate that complement activation has taken place.Activation of complement is controlled at each step in the activation sequence. Eleven distinct proteins with complement regulatory activity have been described. 10Seven of the regulatory proteins are fluid-phase molecules and four are cell membrane glycoproteins. At present, the complement regulatory mechanisms operable in atherosclerotic lesions are unknown. Macrophages, a common component of lesions, possess cell surface complement regulatory molecules 11 -14 ; in addition, they are capa-

Relative Role of Genetic Complement Abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical Phenotype

“…Patients with CFH mutations had a higher incidence of cardiovascular disease (CVD) ( Table 2), which may partly be explained by the higher percentage of patients on dialysis, but a causal link between chronic complement activation and CVD has also been suggested (33).…”

Immunoglobulin treatment reduces atherosclerosis in apo E knockout mice.

“…Lymph node cells and spleen cells were prepared by meshing the tissues on 100-m nylon filters followed by a series of washing steps in DME with 5% FBS (DME-5%). Red blood cells were lysed in the spleen cell preparations with ACK lysing buffer (0.15 M NH 4 Cl, 1 mM KHCO 3 , 0.1 mM Na 2 EDTA, pH 7.3). 300,000 cells/well were plated into 96-well flatbottomed plates in the presence of the following stimuli: Concanavalin A (Con A, 2.5 g/ml; Sigma), oxLDL and native LDL (3.125 and 6.25 g/ml), and ivIg and HSA (20 mg/ml).…”

“…5). Mice treated with ivIg at 0 and 2 mo of diet (the ivIg[0/2-4] group) or only at 2 mo (ivIg [2][3][4]) showed a 50% reduction of lesion formation, with only 6-8% of the cross-section area covered by lesions (Figs. 4 and 5).…”

“…Atherosclerotic plaques are infiltrated by macrophages and T lymphocytes, some of which immunospecifically recognize oxidized LDL (oxLDL) 1 (1), which also accumulate in plaques. Autoantibodies to oxLDL are also found in atherosclerotic plaques (2,3) together with activated components of the complement cascade (4,5). In fact, the titer of auto-antioxLDL may correlate with progression of atherosclerosis in humans (6).…”

Polymorphism of the complement 5 gene is associated with large artery atherosclerosis stroke in Chinese patients

“…All patients received a complete physical examination with a precise record of their medical history. All patients received standardized treatment according to guidelines for the early management of adults who experience IS 7 . Common and internal carotid arteries were investigated for the presence of plaques.…”