Lipid laden macrophages

Dysfunction of the endothelium allows lipoproteins, predominantly low-density lipoprotein (LDL) cholesterol, and inflammatory cells, namely monocytes and T lymphocytes, to migrate from the plasma to the sub-endothelial space. Monocyte-derived macrophages ingest lipoproteins to form foam cells. Macrophages also secrete growth factors that promote smooth muscle cell migration from the media to the intima. A fatty streak consists of lipid-laden macrophages and smooth muscle cells and is the earliest type of atherosclerotic lesion. 

Lipid-laden macrophages, smooth muscle cells, and necrotic debris from the death of foam cells accumulate in the subendothelial space, leading to enlargement of the fatty streak. A collagen matrix forms a fibrous cap that covers the lipid core of the lesion to establish a fibrous plaque called an atherosclerotic plaque. Initially, the diameter of the coronary artery lumen is... 

A thromboembolic diathesis is not unusual and strokes have been reported. Other pathological changes have included microgyri, demyelination, gliosis and brain atrophy. Lipid-laden macrophages have been described. 

CCL2 is present in lipid-laden macrophages and atherosclerotic plaques that are rich in these macrophages. The production of CCL2 in endothelial and smooth muscle cells is stimulated by minimally oxidized low-density lipoproteins (LDLs). As a consequence, CCL2 is involved in the recruitment of foam cells to the vessel... 

The atherosclerotic lesions develop in a complex, chronic process. The first detectable lesion is the so-called fatty streak, an aggregation of lipid-laden macrophage foam cells. The next stage of development is the formation of plaques consisting of a core of lipid and necrotic cell debris covered by a layer of connective tissue and smooth muscle cells. These plaques hinder arterial blood flow and may precipitate clinical events by plaque rupture and thrombus formation. Platelets from the thrombi, activated macrophages, and smooth muscle cells release growth factors and cytokines resulting in an inflammatory-fibroproliferative response that leads to the advanced lesions of atherosclerosis. 

Brain biopsy may show a destructive process within the white matter, with multiple lipid-laden macrophages. 

FIGURE 20.60 Primary demyelination with preservation of brown NF-positive axons. Some axons are swollen and are called spheroids. Lipid-laden macrophages and gliosis are not stained brown in this section of this brain biopsy specimen, but their pale gray features are still evident. 

Homozygotes have elevations of 5 to 6 times than normal Skin xanthomas (collections of lipid-laden macrophage) Xanthelasma around the eyes... 

A major benefit of HDL particles derives from their ability to remove cholesterol from cholesterol-laden cells and to return the cholesterol to the liver, a process known as reverse cholesterol transport. This is particularly beneficial in vascular tissue by reducing cellular cholesterol levels in the subintimal space, the likelihood that foam cells (lipid-laden macrophages that engulf oxidized LDL-cholesterol and represent an early stage in the development of atherosclerotic plaque) will form within the blood vessel wall is reduced. 

Severe hypertriglyceridaemia may be associated with recurrent attacks of abdominal pain and sometimes pancreatitis. This lipid abnormality may interfere with the assay for amylase in some laboratories. Hepatosplenomegaly due to accumulation of lipid-laden macrophages may occur. Rarely there may be memory disturbances and lack of... 

Extrinsic lipoid pneumonia may be caused by aspiration of mineral oil-based laxatives or oil nose drops. Histological findings are charactoistic and show abundance of lipid-laden macrophages. Imaging studies typically show alveolar consolidation in the lower lung zones with low-attenuation infiltrates on the CT scan. 

Acyl-CoA cholesterol acyl transferase (ACAT) catalyzes the intracellular formation of cholesteryl esters (CE) in all mammalian cells. It has been implicated as a key enzyme involved in cholesterol absorption, very low density lipoprotein secretion, and the formation of lipid-laden macrophages. The accumulation of CE in macrophage-derived foam cells is characteristic of the early step in the development of atherosclerosis. ACAT inhibitors reduced TC levels without affecting HDL-C. This can be attributed to decreased intestinal cholesterol absorption based on binding to bile acid (Turley SD. and Herndon MW. 1994)... 

Halpert I, Sires UI, Roby ID, Potter-Perigo S, Wight TN, Shapiro SD, Welgus HG, Wickline SA and Parks WC. Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci USA 93 9748-53, 1996. 

We have recently found, in several expanded PTFE grafts retrieved from humans, atherosclerotic changes in the neointima which are independent of the anastomoses. Unlike the thin, smooth neointima which usually develops in these grafts and appears to be fibrin, the focal areas of atherosclerosis show cellular proliferation with microfoci of hypocellularity, cellular degeneration, focal calcification and lipid-laden macrophages. These histologic changes are consistent with the early atherosclerotic lesion. 

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