Scavenger activity in monocyte-derived macrophages from atherothrombotic strokes.

Abstract

Foam cells are lipid-laden macrophages derived primarily from circulating mononuclear cells and are a characteristic feature of atheromatous lesions. The exact role of these foam cells in the pathogenesis of atherosclerotic lesions remains uncertain, but one potential function is to take-up and process excess interstitial arterial lipoproteins, suggested by their extraordinary ability to engulf enormous quantities of modified low density lipoproteins by the so-called "scavenging pathway." To test this possibility, monocytes from 15 atherothrombotic brain infarct patients and age and sex matched controls were isolated and cultured for 7-8 days in 20% normal serum. The monocyte-derived macrophages were investigated for their ability to bind, internalize and degrade both native and modified (acetylated) LDL labelled with 125Iodine. While native LDL was metabolized similarly, stroke macrophages displayed significantly reduced ability to scavenge modified LDL. These findings suggest that insufficient processing of interstitial arterial cholesterol by monocyte-derived macrophages may contribute to the aggravation of atheroma formation. This inadequacy is likely further compromised by reduced levels of serum high density lipoprotein since the absence of a cholesterol-acceptor will promote the slow but continued accumulation of lipids and the formation of foam cells.