DISTRIBUTION OF IMMUNOGLOBULIN SUPERFAMILY MEMBERS ICAM-1, ICAM-2, ICAM-3, AND THE BETA-2 INTEGRIN LFA-1 IN MULTIPLE-SCLEROSIS LESIONS

To identify potential molecular substrates for leukocyte trafficking a nd activation in multiple sclerosis (MS) brain, we determined the immu nocytochemical distribution of the beta(2) integrin lymphocyte-functio n-associated antigen-1 (LFA-1) and its major ligands, intercellular ad hesion molecule (ICAM)-1, ICAM-2, and ICAM-3 in MS tissue. Colocalizat ion of these adhesion molecules with lineage-specific markers was anal yzed by dual-labeling immunocytochemisty and confocal microscopy. ICAM -1 and ICAM-2 were detected on endothelial cells, and ICAM-3 immunorea ctivity was restricted to infiltrating leukocytes. In control brain, 1 0% of glucose transporter-1-positive vessels contained ICAM-1 immunore activity on their luminal surface and 21% were ICAM-2-positive. A sign ificant increase in ICAM-1-positive vessels was found in MS brains. Th is increase was greater in MS lesions (81% of vessels) than in nonlesi on areas (37% of vessels). A significant increase in ICAM-1-positive v essels 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 I CAM-3 and LFA-1 were detected on the vast majority of infiltrating lym phocytes and monocytes in and near MS lesions, and these cells were of ten 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-posit ive microglia. These results suggest a role for ICAM-1, -2, and LFA-1 in the transendothelial migration of leukocytes into MS brain and a ro le for ICAM-3/LFA-1 interactions in the activation of lymphocytes, mon ocytes, and microglia in MS lesions.