Identification of macrophages and smooth muscle cells with monoclonal antibodies in the human atherosclerotic plaque

Abstract

Sections of human atherosclerotic plaques, obtained from 21 autopsy cases with various degrees of atherosclerosis, were stained with the indirect immunoperoxidase technique using specific monoclonal antibodies against macrophages and smooth muscle cells. Distinctive results were found in differing stages: Single blood monocytes were observed in diffuse intimal thickening and the foam cells seen in fatty streaks were mostly identified as mature tissue macrophages, while only very few blood monocytes were present. The spindle cells observed in fibroelastic plaques showed positive reactions to antibodies against desmin, which points to their derivation from smooth muscle cells, whereas only a few macrophage-derived foam cells were seen in these lesions. In the complicated lesions the majority of foam cells were macrophage-derived, but there was also a small number of foam cells positive to antibodies against desmin, suggesting a smooth muscle cell derivation. Our results confirm that in human atherosclerotic plaques the majority of the foam cells are obviously macrophage-derived, which emphasizes the important role of macrophages in the morphogenesis of these lesions.

The immunohistochemical heterogeneity of atheroma macrophages: comparison with lymphoid tissues suggests that recently blood-derived macrophages can be distinguished from longer-resident cells.

“…A previous study on atherosclerosis with the 27E10 antibody produced similar results to the RBDMph group shown here and came to the same conclusions (43). The maximal subendothelial staining ofthe RBD-Mph markers and their contrast with the remainder of the panel correlates excellently with the view that the majority of Mphs enter an atherosclerotic lesion at the luminal surface from the blood and subsequently migrate outwards through the wall.…”

“…It therefore appears that the RBD-Mph markers, despite being expressed well on monocytes, are lost at variable rates on migration of the cells into the tissues. MAC387 reacts with the p8/14 molecule (calgranulin), and another antibody, 27E10, against this protein has given similar staining of Mph populations (42,43). Moreover, this protein, and in particular the 14 KD component with which MAC387 reacts, has been shown to be expressed maximally at an early stage of monocyte-Mph differentiation and is absent at later stages (44).…”

Is Overamplification of the Normal Macrophage Defensive Role Critical to Lesion Development?a

“…This is suggested by an immunohistochemical study of human aorta and coronary and carotid arteries, which evaluated the differentiation state of monocytes in diffuse intimal thickening, fatty streaks, and atheromatous plaques 9 . These observations and others 10,11 suggest a gradual shift toward a more differentiated phenotype with presumably longer residence time within the lesion. Some studies suggest that there may be selective activation of macrophage functions, sometimes associated with different stages of lesion development.…”

Inflammation, Lipids, and Free Radicals: Lessons Learned from the Atherogenic Process

“…The initiation and progression of the lesions involves cellular migration and proliferation and the production of a significant number of pro-inflammatory factors such as chemokines, cytokines, and growth factors by all of the cell types within the artery wall. [1][2][3][4][5] It is still largely unknown how the cells are activated to proliferate and pro duce these proatherogenic factors, but recent evi dence suggests that oxidative stress contributes to the stimulation of cell division, gene expression, and cell death. [6][7][8][9] Oxidative stress is a widely used, ambiguous term that generally refers to an imbal ance in the rate at which the intracellular content of free radicals increases relative to the capacity of the cell to eliminate free radicals.…”