Alpha4-integrin-VCAM-1 binding mediates G protein-independent capture of encephalitogenic T cell blasts to CNS white matter microvessels.
Direct in vivo evidence is still lacking for alpha4-integrin-mediated T cell interaction with VCAM-1 on blood-brain barrier-endothelium in experimental autoimmune encephalomyelitis (EAE). To investigate a possible alpha4-integrin-mediated interaction of encephalitogenic T cell blasts with VCAM-1 on the blood-brain barrier white matter endothelium in vivo, we have developed a novel spinal cord window preparation that enabled us to directly visualize CNS white matter microcirculation by intravital fluorescence videomicroscopy. Our study provides the first in vivo evidence that encephalitogenic T cell blasts interact with the spinal cord white matter microvasculature without rolling and that alpha4-integrin mediates the G protein-independent capture and subsequently the G protein-dependent adhesion strengthening of T cell blasts to microvascular VCAM-1.
Vajkoczy
P
P
Department of Neurosurgery, Klinikum Mannheim, Universität Heidelberg, Mannheim, Germany.
Laschinger
M
M
Engelhardt
B
B
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001812:Blood-Brain Barrier / Q000502:physiology*; D002196:Capillaries / Q000473:pathology; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D039441:Integrin alpha4; D051379:Mice; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D020721:Nervous System Autoimmune Disease, Experimental; D011485:Protein Binding; D012884:Skin Window Technique; D013116:Spinal Cord / Q000098:blood supply* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000378:metabolism* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000235:genetics / Q000494:pharmacology
D015703:Antigens, CD; D019010:Vascular Cell Adhesion Molecule-1; D010566:Virulence Factors, Bordetella; D039441:Integrin alpha4; D019204:GTP-Binding Proteins