Laminin, a major glycoprotein component of vessel basement membranes, is recognized by β1- and β3-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 β1 subunits were decreased compared to controls whereas α(v) subunit and VLA-1 were increased. In chronic inactive lesions β1, VLA-6 and α(v) were the same as controls but VLA-1 remained increased. α3 subunit was constant in all samples. By immunoelectron microscopy VLA-1, VLA-6, β1, and laminin were distributed throughout endothelial cells; α(v) was adjacent to and on luminal surfaces; α(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 β1/VLA-6 could result in their detachment from laminin thereby facilitating leukocyte transvascular migration and blood-brain barrier breakdown. α(v) and VLA-1 on intercellular junctions may participate in re-establishing vessel integrity after leukocyte migration. Luminal surface α(v) also likely binds intraluminal ligands and cells. In chronic inactive plaques persistently elevated endothelial cell VLA-1 correlates with longstanding endothelial cell and blood-brain barrier dysfunction.
Sobel, R. A., Hinojoza, J. R., Maeda, A., & Chen, M. (1998). Endothelial cell integrin laminin receptor expression in multiple sclerosis lesions. American Journal of Pathology, 153(2), 405–415. https://doi.org/10.1016/S0002-9440(10)65584-8