Abstract |
To identify potential molecular substrates for leukocyte trafficking and activation in multiple sclerosis (MS) brain, we determined the immunocytochemical distribution of the beta, integrin lymphocyte-function-associated antigen-1 (LFA-1) and its major ligands, intercellular adhesion molecule (ICAM)-1, ICAM-2, and ICAM-3 in MS tissue. Colocalization of these adhesion molecules with lineage-specific markers was analyzed by dual-labeling immunocytochemistry and confocal microscopy. ICAM-1 and ICAM-2 were detected on endothelial cells, and ICAM-3 immunoreactivity was restricted to infiltrating leukocytes. In control brain, 10% of glucose transporter-1 positive vessels contained ICAM-1 immunoreactivity on their luminal surface and 21% were ICAM-2-positive. A significant increase in ICAM-1-positive vessels was found in MS brains. This increase was greater in MS lesions (81% of vessels) than in nonlesion areas (37% of vessels). A significant increase in ICAM-1-positive vessels was found in encephalitis (55% of vessels) but not in Parkinson's (17% of vessels) brains. The percentage of vessels expressing ICAM-2 was not increased in MS, encephalitis, or Parkinson's brains. Both ICAM-3 and LFA-1 were detected on the vast majority of infiltrating lymphocytes and monocytes in and near MS lesions, and these cells were often closely apposed to each other. In addition, LFA-1 was detected on activated microglia located close to the edge of demyelinating lesions. ICAM-3-positive leukocytes were often closely apposed to LFA-1-positive microglia. These results suggest a role for ICAM-1, -2, and LFA-1 in the transendothelial migration of leukocytes into MS brain and a role for ICAM 3/LFA-1 interactions in the activation of lymphocytes, monocytes, and microglia in MS lesions.
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Authors | L Bö, J W Peterson, S Mørk, P A Hoffman, W M Gallatin, R M Ransohoff, B D Trapp |
Journal | Journal of neuropathology and experimental neurology
(J Neuropathol Exp Neurol)
Vol. 55
Issue 10
Pg. 1060-72
(Oct 1996)
ISSN: 0022-3069 [Print] England |
PMID | 8858003
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antigens, CD
- Antigens, Differentiation
- Cell Adhesion Molecules
- ICAM2 protein, human
- ICAM3 protein, human
- Lymphocyte Function-Associated Antigen-1
- Intercellular Adhesion Molecule-1
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Antigens, CD
(analysis)
- Antigens, Differentiation
- Brain
(cytology, immunology)
- Brain Chemistry
- Cell Adhesion Molecules
(analysis)
- Child
- Child, Preschool
- Endothelium
(chemistry, cytology)
- Humans
- Infant
- Infant, Newborn
- Intercellular Adhesion Molecule-1
(analysis)
- Leukocytes
(chemistry)
- Lymphocyte Function-Associated Antigen-1
(analysis)
- Microscopy, Confocal
- Middle Aged
- Multiple Sclerosis
(immunology, metabolism)
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