Ultrastructural localization of tissue factor on monocyte-derived macrophages and macrophage foam cells associated with atherosclerotic lesions
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S C Landers1, M Gupta, J C Lewis
1Department of Pathology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1092.
Abstract:
The expression of tissue factor (TF) antigen by circulating monocytes, cultured macrophages, and macrophages associated with atherosclerotic lesions was ultrastructurally analysed using immunogold labeling. A subpopulation of macrophages associated with the intimal surface overlying lesions had a significant TF expression. Macrophages and macrophage foam cells that projected from the intima into the arterial lumen also expressed a high level of TF (14-fold increase over control). In contrast, circulating monocytes and macrophages in culture did not express TF above background control levels. This TF expression by macrophages in vivo but not by macrophages cultured from either normal or hypercholesterolemic animals suggests that monocyte activation and macrophage transition, as measured by TF expression, is lesion-dependent and not stimulated solely by intimal attachment, surface migration, or hypercholesterolemia. These results further suggest that macrophages and foam cells associated with early lesions of atherosclerosis can initiate fibrin formation, which could contribute to lesion complications and transition to a fibromuscular stage.
Insights
Macrophages in atherosclerotic lesions express high levels of tissue factor (TF), initiating fibrin formation. This TF expression is lesion-dependent, not solely due to hypercholesterolemia or cell migration.
Area of Science:
- Vascular Biology
- Immunohistochemistry
- Atherosclerosis Research
Background:
- Tissue factor (TF) is a key initiator of the coagulation cascade.
- Macrophage TF expression is implicated in atherogenesis, but its regulation in vivo is unclear.
Purpose of the Study:
- To ultrastructurally analyze TF antigen expression in macrophages within atherosclerotic lesions.
- To determine if TF expression is dependent on lesion presence, hypercholesterolemia, or cell culture conditions.
Main Methods:
- Immunogold labeling was used for ultrastructural analysis of TF antigen.
- Circulating monocytes, cultured macrophages, and macrophages from atherosclerotic lesions were examined.
Main Results:
- Macrophages and foam cells at the intimal surface and projecting into the lumen of atherosclerotic lesions showed significant TF expression (up to 14-fold increase).
- Circulating monocytes and cultured macrophages (from normal or hypercholesterolemic animals) did not exhibit elevated TF expression.
- TF expression was found to be lesion-dependent, not solely stimulated by intimal attachment, migration, or hypercholesterolemia.
Conclusions:
- Macrophages within atherosclerotic lesions, but not circulating monocytes or cultured macrophages, express high levels of TF.
- Lesion-associated macrophages and foam cells can initiate fibrin formation, potentially contributing to atherosclerosis progression and complications.