Role of the ICAM-1/LFA-1 pathway during the development of autoimmune dacryoadenitis in an animal model for Sjögren's syndrome.
We have analyzed the role of cell adhesion molecules during the development of autoimmune dacryodenitis in an NFS/sld mouse model for primary Sjögren's syndrome. The expression of cell adhesion molecules was assessed by RT-PCR and immunohistochemistry. We detected an up-regulation of local cell adhesion molecule genes (ICAM-1, LFA-1, CD44 and Mel-14) in the course of autoimmune lacrimal gland diseases. Immunohistochemically, ICAM-1 was localized exclusively in the endothelial cells of variously sized blood vessels before the onset of disease, and LFA-1, CD44 and Mel-14, expressing infiltrating cells, were found within these lesions. When the therapeutic effects of blocking cell adhesion molecules in vivo were examined, antibodies to ICAM-1 in combination with anti-LFA-1 prevented the development of autoimmune lacrimal gland diseases in NFS/sld mice. These data suggest that in Sjögren's syndrome-like autoimmune dacryoadenitis in NFS/sld mutant mice, the ICAM-1/LFA-1 pathway may play a crucial role in the development and subsequent progression of T-cell-mediated autoimmunity in the lacrimal glands.
Takahashi
M
M
Department of Ophthalmology, School of Medicine, University of Tokushima, Japan.
Mimura
Y
Y
Hayashi
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000502:physiology; D003607:Dacryocystitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D012859:Sjogren's Syndrome / Q000209:etiology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1