Formation and involution of Mallory bodies ("alcoholic hyalin") in murine and human liver revealed by immunofluorescence microscopy with antibodies to prekeratin

Abstract

Antibodies raised against prekeratin intensely and specifically stain, in immunofluorescence microscopy, Mallory bodies ("alcoholic hyalin") present in livers of human alcoholics and griseofulyin-treated mice. The high sensitivity of this method allows the identification of small distinct cytoplasmic structures that are observed during early stages of Mallory body formation, especially frequent in the perinuclear cytoplasm, as well as during stages of Mallory body disintegration and disappearance, such as after withdrawal of the drug. In the latter situation, the prekeratin-containing small particles exhibit a characteristic pattern of arrangement in the hepatocyte periphery. Electron microscopy illustrates that such small bodies are heap-like aggregates of typical Mallory body filaments. Immunofluorescence studies with antibodies to isolated prekeratin polypeptides from bovine hoof or muzzle epidermis show that Mallory body filaments, in particular those in human liver, are immunologically more closely related to prekeratin of tonofilaments from living epidermal cells (stratum spinosum). The data indicate that Mallory bodies contain a pathologic form of prekeratin-like material. They also suggest that disorders of cytoskeletal structures of the intermediate-sized filament class are associated with specific diseases and can be visualized and characterized by immunofluorescence microscopy by using antibodies to constitutive proteins of such filaments.