Adhesion molecules as susceptibility factors in spontaneous autoimmune thyroiditis in the NOD-H2h4 mouse.
Mononuclear cell infiltration of the thyroid is a prominent feature of chronic lymphocytic thyroiditis. Adhesion molecules play a major role in determining the localization of inflammatory mononuclear cells in the thyroid. Previous reports from animal models and human studies have described the thyroidal expression of adhesion molecules only late in clinical disease. In this study, we examined the distribution and kinetics of expression of E-selectin, VCAM-1, LFA-1, and ICAM-1 in the NOD-H2h4 mouse, a model of spontaneous autoimmune thyroiditis accelerated by dietary iodine. Mice were fed 0.015% NaI in their drinking water for 2, 4, 6, 8, and 16 weeks, and thyroids were removed, serially sectioned, and stained in an avidin-biotin-peroxidase assay. We found a dramatic increase in E-selectin and VCAM-1 expression on intrathyroidal endothelial cells after 16 weeks of iodine treatment. In addition, we describe for the first time that thyrocytes from the NOD-H2h4 mouse, and the parental NOD, constitutively express ICAM-1 independent of iodine treatment and prior to mononuclear cell infiltration of the thyroid gland. ICAM-1 was not detected on the thyrocytes of other untreated strains of mice, implicating expression of this adhesion molecule as a critical event in the recruitment of inflammatory mononuclear cells to the thyroid.
Bonita
Raphael E
RE
Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Rose
Noel R
NR
Rasooly
Linda
L
Caturegli
Patrizio
P
Burek
C Lynne
CL
D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D019040:E-Selectin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D012974:Sodium Iodide / Q000008:administration & dosage; D013961:Thyroid Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D019040:E-Selectin; D016169:Lymphocyte Function-Associated Antigen-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D012974:Sodium Iodide