Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system
R A Sobel1, M E Mitchell, G Fondren
1Department of Pathology, Massachusetts General Hospital, Boston.
Insights
Intercellular adhesion molecule-1 (ICAM-1) expression on central nervous system (CNS) vessels increases during inflammation. This molecule may promote leukocyte infiltration into the CNS, contributing to diseases like multiple sclerosis (MS).
Area of Science:
- Neuroimmunology
- Cellular and Molecular Neuroscience
- Pathology of the Central Nervous System
Background:
- Intercellular adhesion molecule-1 (ICAM-1) is involved in immune cell adhesion and migration.
- The role of ICAM-1 and its ligand, lymphocyte function-associated molecule-1 (LFA-1), in central nervous system (CNS) inflammatory conditions is not fully understood.
- Understanding ICAM-1 expression in CNS lesions is crucial for deciphering leukocyte trafficking in neurological diseases.
Purpose of the Study:
- To investigate the expression patterns of ICAM-1 and LFA-1 in postmortem human CNS tissue.
- To correlate ICAM-1 expression with different neuropathological conditions, including multiple sclerosis (MS) and inflammatory lesions.
- To elucidate the potential role of ICAM-1/LFA-1 interactions in leukocyte infiltration into the CNS.
Main Methods:
- Immunohistochemical staining of cryostat sections from human CNS tissue.
- Antibodies used targeted ICAM-1 and LFA-1.
- Tissue samples included multiple sclerosis (MS) cases, inflammatory/necrotic lesions, and normal controls.
Main Results:
- ICAM-1 expression was observed on CNS microvessels in normal controls, with increased expression in active MS plaque edges, viral encephalitis, and infarcts.
- Mononuclear cells and some glia within active MS plaques and viral infections showed ICAM-1 positivity.
- LFA-1 was positive on mononuclear cells but not on CNS resident cells, suggesting LFA-1 mediates interactions with inflammatory cells.
Conclusions:
- CNS vessel ICAM-1 expression is variable in normal tissue but increases focally during immune reactions.
- ICAM-1, through binding with LFA-1 on leukocytes, likely promotes the influx of inflammatory cells into the CNS.
- Parenchymal ICAM-1 expression may indicate additional interactions with inflammatory cells in diverse CNS lesions.
Abstract:
Cryostat sections of human central nervous system (CNS) tissue samples from 10 cases of multiple sclerosis (MS), 11 cases with inflammation and necrosis, and 24 normal controls were immunostained with antibodies to intercellular adhesion molecule-1 (ICAM-1) and its integrin ligand lymphocyte function-associated molecule-1 (LFA-1). In 18 controls, small numbers of CNS microvessels were ICAM-1-positive. There were more numerous ICAM-1-positive vessels in active MS plaque edges, viral encephalitis lesions, infarcts, and in six controls. Within active MS plaques and in viral infections, mononuclear cells and some glia also were ICAM-1-positive. Mononuclear but not CNS resident cells were LFA-1-positive. Thus, CNS vessel ICAM-1 expression is variable in amount in postmortem samples of normal human CNS tissue, may increase early and focally in cellular immune reactions, and, via binding of LFA-1, may promote leukocyte influx into the CNS. Intercellular adhesion molecule-1 expression on parenchymal cells may indicate additional interactions with LFA-1 on inflammatory cells in diverse CNS lesions.
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