Endothelial cell integrin laminin receptor expression in multiple sclerosis lesions.
Laminin, a major glycoprotein component of vessel basement membranes, is recognized by beta1- and beta3-integrins expressed on endothelial cells. To determine how endothelial cell integrins might function in multiple sclerosis (MS) lesions, integrin laminin receptors and laminin were analyzed in central nervous system samples from MS patients and controls by immunohistochemistry. In active MS lesions, endothelial cell VLA-6 and beta1 subunits were decreased compared to controls whereas alpha(v) subunit and VLA-1 were increased. In chronic inactive lesions beta1, VLA-6 and alpha(v) were the same as controls but VLA-1 remained increased. Alpha3 subunit was constant in all samples. By immunoelectron microscopy VLA-1, VLA-6, beta1, and laminin were distributed throughout endothelial cells; alpha(v) was adjacent to and on luminal surfaces; alpha(v) and VLA-1 were on intercellular junctions. These results indicate distinct regulation and functions of these integrins in different lesion stages. In active lesions decreased endothelial cell beta1/VLA-6 could result in their detachment from laminin thereby facilitating leukocyte transvascular migration and blood-brain barrier breakdown. Alpha(v) and VLA-1 on intercellular junctions may participate in re-establishing vessel integrity after leukocyte migration. Luminal surface alpha(v) also likely binds intraluminal ligands and cells. In chronic inactive plaques persistently elevated endothelial cell VLA-1 correlates with long-standing endothelial cell and blood-brain barrier dysfunction.
Pathology Service, Veterans Affairs Health Care System, Palo Alto, California 94304, USA.
R A
RA
Sobel
J R
JR
Hinojoza
A
A
Maeda
M
M
Chen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis; D002490:Central Nervous System / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007231:Infant, Newborn; D039222:Integrin alpha1beta1; D039421:Integrin alpha2; D039422:Integrin alpha3; D039121:Integrin alpha6beta1; D039564:Integrin alphaV; D019012:Integrin beta1 / Q000096:biosynthesis; D016023:Integrins / Q000096:biosynthesis; D007797:Laminin / Q000096:biosynthesis; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism*; D017474:Receptors, Laminin / Q000096:biosynthesis*
D015703:Antigens, CD; D039222:Integrin alpha1beta1; D039421:Integrin alpha2; D039422:Integrin alpha3; D039121:Integrin alpha6beta1; D039564:Integrin alphaV; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D017474:Receptors, Laminin