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Fibronectin in multiple sclerosis lesions
1Immunopathology Unit, Massachusetts General Hospital, Boston 02114.
Abstract:
Cryostat sections of central nervous system (CNS) tissues of patients with multiple sclerosis (MS) and other CNS diseases were stained with antibodies to fibronectin, a macrophage fibronectin receptor component, fibrin/fibrinogen, and albumin using immunoperoxidase. In active, but not inactive, MS plaques vessel fibronectin was increased (to approximately 57% of Factor VIII+ vessels) over uninvolved MS and normal control white matter (P less than 0.001 for both). Fibronectin was primarily localized to vessel walls and amount of staining correlated with degree of inflammation. Active plaques and necrotic lesions also had extracellular fibronectin and fibrin/ogen. These molecules and the fibronectin receptor were found on macrophages. Albumin was more widely and diffusely distributed in lesions than fibronectin. Thus, in addition to extravasation from damaged vessels, fibronectin may be deposited on or synthesized by endothelial cells and macrophages in the CNS. Fibronectin could facilitate monocyte adhesion to endothelial cell luminal surfaces, promote migration of mononuclear cells, and enhance myelin phagocytosis in MS lesions.
Insights
Fibronectin accumulates in active multiple sclerosis (MS) lesions, particularly in blood vessel walls. This protein may play a role in the inflammatory and repair processes within the central nervous system (CNS) during MS.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS).
- The role of extracellular matrix proteins like fibronectin in MS pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the presence and localization of fibronectin and related molecules in MS lesions.
- To explore the potential functions of fibronectin in the inflammatory processes of MS.
Main Methods:
- Immunoperoxidase staining of cryostat sections from CNS tissues of MS patients and controls.
- Antibodies used targeted fibronectin, macrophage fibronectin receptor, fibrin/fibrinogen, and albumin.
- Quantification of fibronectin in relation to Factor VIII+ vessels in active MS plaques.
Main Results:
- Increased vessel fibronectin in active MS plaques compared to inactive plaques and normal white matter.
- Fibronectin localized to vessel walls, correlating with inflammation severity.
- Extracellular fibronectin and fibrin/ogen found in active plaques and necrotic lesions.
- Macrophages identified as expressing fibronectin and its receptor.
- Albumin showed wider distribution than fibronectin in lesions.
Conclusions:
- Fibronectin deposition in MS lesions may involve endothelial cells and macrophages, not just extravasation.
- Fibronectin may contribute to monocyte adhesion, mononuclear cell migration, and myelin phagocytosis in MS.
- These findings highlight fibronectin's potential role in MS immunopathology and repair mechanisms.
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