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.

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