Lymphocyte binding to vascular endothelium in inflamed skin revisited: a central role for vascular adhesion protein-1 (VAP-1).
The binding of leukocytes to vascular endothelium and their migration into tissues is mediated by adhesion molecules on the endothelial cells and leukocytes. Vascular adhesion protein-1 (VAP-1) is a 170-180/90-kDa endothelial molecule expressed most prominently in high endothelial venules in peripheral lymph node (PLN) type lymphatic tissues. VAP-1 mediates lymphocyte binding to PLN, tonsil and synovium. The expression of VAP-1 is induced in inflammatory diseases such as arthritis and gut inflammation. We examined the expression, structure and function of VAP-1 in normal and inflamed skin and compared it to those of other adhesion molecules implicated in skin homing. In psoriasis lichen ruber planus, pemphigoid and allergic lesions, VAP-1 was markedly upregulated. The expression of VAP-1 was also increased in biopsies of healthy skin of the patients. The VAP-1 molecule induced in skin is decorated with abundant sialic acids. VAP-1 inflamed skin is functional, since inhibition with anti-VAP-1 monoclonal antibodies caused a 60% reduction in lymphocytes adhesion to vascular endothelium. Antibodies against E-selectin, which has been regarded as the major vascular addressin directing cutaneous lymphocyte traffic, and, surprisingly, against peripheral lymph node addressin (PNAd), caused inhibitions of 30% and 60%, respectively, in the frozen section adhesion assay. These findings suggest important roles also for VAP-1 and PNAd in lymphocyte homing into inflamed skin.
Arvilommi
A M
AM
National Public Health Institute, Finland. anna-maija.arvilommi@utu.fi
Salmi
M
M
Kalimo
K
K
Jalkanen
S
S
D006631:Amine Oxidase (Copper-Containing); D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D000954:Antigens, Surface / Q000502:physiology; D001706:Biopsy; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D003872:Dermatitis / Q000276:immunology*; D017449:Dermatitis, Allergic Contact / Q000276:immunology / Q000473:pathology; D019040:E-Selectin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008010:Lichen Planus / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins; D010391:Pemphigoid, Bullous / Q000276:immunology / Q000473:pathology; D011565:Psoriasis / Q000276:immunology / Q000473:pathology; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C063419:CTAGE1 protein, human; D015815:Cell Adhesion Molecules; D019040:E-Selectin; C069886:L-selectin counter-receptors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012795:Sialoglycoproteins; D018799:Intercellular Adhesion Molecule-1; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)