Activation of complement by cytoskeletal intermediate filaments

Abstract

INTEREST in cytoplasmic intermediate (10 nm) filaments has grown since the successful immunohistochemical differentiation of these filaments from microtubules and microfilaments^1,2. Despite the widespread occurrence of intermediate filaments in various cell types, little is known about their function^1,3,4. A cytoskeletal nucleus-anchoring role has been suggested based on their intracellular distribution, their connections to the Plasma membrane and nucleus, and their marked insolubility in detergents and salt solutions^5,6. The presence of autoantibodies against intermediate filaments in the sera of patients^7,8 suggests that these filaments can be involved in pathogenetic processes. We report here that in studies on possible pathogenetic mechanisms involving intermediate filaments, antibody-independent binding of complement components to intermediate filaments has been observed. Initial observations were made using cultured human embryonal fibroblasts, as cytoplasmic filaments present in these cells have been characterised by using both immunological markers and drugs capable of selectively altering the morphology of microfilaments, intermediate filaments and microtubules^1,7. Subsequent studies showed complement binding to similar cytoplasmic structures of other cultured cells and also cells in tissue sections.