Systemic Clearance of Radiation-Induced Apoptotic Cells by SIGN-R1 and Complement Factors and their Involvement in Autoimmune Diseases

Abstract

Although ionizing radiation has been used for treating a variety of human cancers, radiotherapy inadvertently results in the damage of normal tissues, functionally altering the immune system and being able to cause various organ specific autoimmune diseases. Macrophages and complements play pivotal roles in the clearance of the apoptotic cells, facilitating their opsonindependent phagocytosis and systemic clearance of apoptotic cells. SIGN-R1, a membrane bound C-type lectin expressed on the splenic marginal macrophages, mediates a classical but Ig-independent complement activation pathway by interacting with C1q, and SIGN-R1 and complement factors might play the integral role in the clearance of radiation-induced apoptotic cells. Also, DC-SIGN, the human homolog of SIGN-R1 on dendritic cells and macrophage subpopulations, directly binds to C1q, probably providing an initiation site for the classical complement pathway in the presence of a pathogenic surface. Autoimmune diseases are becoming a serious public health problems and there is increasing evidence that C-type lectins and complement system are involved in the pathogenesis of the autoimmune diseases. Therefore, further works are required to identify the existence of diverse membranebound C-type lectins that could mediate complement activation against apoptotic cells in vivo and its involvement in the pathogenesis of the autoimmune diseases.