Expression and function of membrane attack complex inhibitory proteins on thyroid follicular cells.
Human thyroid cells are resistant to lysis by the homologous membrane attack complex. By immunohistochemical staining we here show that normal thyroid cells and those in Graves' disease and Hashimoto's thyroiditis express two membrane attack complex-inhibiting proteins, CD59 antigen and membrane attack complex-inhibiting protein/homologous restriction factor (MIP/HRF). In vitro, the expression of both molecules was enhanced by interleukin-1 (IL-1), tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) and cytokine-treated thyroid cells were more resistant to lysis by homologous complement. Blocking experiments with monoclonal antibodies against CD59 antigen and MIP/HRF showed that both molecules contributed but CD59 antigen was the more important in mediating resistance to complement attack. Expression of these proteins may be an important determinant of the severity of tissue injury produced by complement-fixing thyroid peroxidase antibodies in autoimmune thyroid disease.
Department of Medicine, University of Sheffield Clinical Sciences Centre, Northern General Hospital, U.K.
N
N
Tandon
B P
BP
Morgan
A P
AP
Weetman
D015703:Antigens, CD / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis; D015153:Blotting, Western; D018957:CD59 Antigens; D002352:Carrier Proteins / Q000032:analysis; D002462:Cell Membrane / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D015938:Complement Membrane Attack Complex / Q000037:antagonists & inhibitors*; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis; D011506:Proteins / Q000032:analysis; D013961:Thyroid Gland / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
D015703:Antigens, CD; D001798:Blood Proteins; D018957:CD59 Antigens; D002352:Carrier Proteins; D015938:Complement Membrane Attack Complex; D008562:Membrane Glycoproteins; D011506:Proteins; C051590:CD59 protein, human