Homing of mucosal leukocytes to joints. Distinct endothelial ligands in synovium mediate leukocyte-subtype specific adhesion.
Inflammation and infection of the gut can be followed by reactive arthritis at a distant joint. Leukocyte recruitment into synovium is essential for this process, but nothing is known about the endothelial adhesion molecules in synovial membrane which direct the homing of activated, gut-derived leukocytes to joints. Here we analyzed the expression of the known endothelial adhesion molecules in inflamed synovium and their function in binding of mucosal leukocytes. Intercellular adhesion molecule-1 (ICAM-1/CD54) and vascular adhesion protein-1 (VAP-1) were most prominently expressed in synovial vessels. All other adhesion molecules were found at lower levels in inflamed synovia, except mucosal addressin which was absent. Binding of macrophages isolated from lamina propria of the gut to synovial endothelium was almost entirely P-selectin-dependent. In contrast, small intestinal lymphocytes and immunoblasts both relied mainly on VAP-1 in recognition of synovial vessels. Thus, endothelial P-selectin and VAP-1 mediate binding of mucosal effector cells to synovium in a leukocyte subtype-selective manner. Antiadhesive therapy against these inducible molecules should ablate the pathogenetic cascade leading to inappropriate homing of leukocytes to joints in arthritis.
Salmi
M
M
National Public Health Institute, and MediCity Research Laboratory, Turku University, Finland. marko.salmi@utu.fi
Rajala
P
P
Jalkanen
S
S
D006631:Amine Oxidase (Copper-Containing); D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D016918:Arthritis, Reactive / Q000209:etiology*; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000276:immunology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000276:immunology; D007962:Leukocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins; D009088:Mucoproteins / Q000096:biosynthesis / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology; D019087:Selectins / Q000096:biosynthesis / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology* / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C069886:L-selectin counter-receptors; C504265:MADCAM1 protein, human; D008565:Membrane Proteins; D009088:Mucoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019087:Selectins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)