Interaction of alpha4-integrin with VCAM-1 is involved in adhesion of encephalitogenic T cell blasts to brain endothelium but not in their transendothelial migration in vitro.
Based on the observation that antibodies directed against alpha4-integrin and its counterreceptor VCAM-1 inhibit inflammatory cell recruitment into the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE), it has been concluded that alpha4-integrin/VCAM-1 interaction plays a critical role in T cell interaction with the blood-brain barrier (BBB) endothelium. In order to define the exact role of alpha4-integrin and VCAM-1 in T cell recruitment across the BBB endothelium we set up in vitro studies, where we investigated the interaction of freshly activated autoaggressive T cell blasts with the brain endothelial cell line bEnd5. A large panel of blocking antibodies directed against the alpha4-, beta1- and beta7-integrin subunits or against the alpha4beta7-heterodimer and against endothelial VCAM-1 significantly reduced adhesion of encephalitogenic T cell blasts to brain endothelium. However, the very same antibodies did not influence transendothelial migration of autoaggressive T cell blasts across a bEnd5 monolayer. Our in vitro observations, therefore, suggest that in vivo alpha4/VCAM-1 interactions are not involved in transendothelial migration of encephalitogenic T cells across the BBB but rather mediate earlier steps of T cell/BBB-interaction such as firm adhesion.
Laschinger
M
M
Max-Planck-Institut für Physiologische und Klinische Forschung, Bad Nauheim, Germany.
Engelhardt
B
B
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism; D002560:Cerebrovascular Circulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D012016:Reference Values; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism / Q000502:physiology*
D015703:Antigens, CD; D039041:Integrin alpha4beta1; D016023:Integrins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; C071777:integrin alpha4beta7; C435023:myelin proteolipid protein (139-151); D039441:Integrin alpha4