Effect Of Anti-keratin 16 Monoclonal Autoantibody On The Proliferation Of Human Malignant Keratinocyte And Its Molecular Mechanism

Keratins are a-helix proteins, and so far more than thirty kinds of keratin have been discovered. Different keratins have different molecualr weights. They are encoded by different genes and produced by epithelial cells in different phases of growth and differentiation. Thus, keratins are regarded as molecular markers of different phases in epithelial differentiation. Keratinocyte (KC) is the major cell of epedermis, and its defferentiation is of great importance to the normal function of epidermis. KC differentiation is accompanied by changing expression of various keratins. Keratin I (Kl and KlO in superbasal layer are generally referred to as markers of normal differentiation, while K6 and K16 are charateristic of epidermal hyper-proliferation and the activation of KC. Anti-keratin antoantibodies (AK auto Ab), the antibodies against keratins of different molecular weights, generally exist in normal human bodies and contain three classes of antibody --- IgA, IgG and 1gM. Previous research has achieved a rather deep understanding of the biological property and function of AK auto Ab. With indirect immunofluorescence (hF) and enzyme-linked immunosorbnent assay (ELISA), AK auto Ab were detected in virtually all the normal human sera. According to their different stained locatkons on the epidermis, Iwatsuki et at divided human -8- serum samples into five groups and studied the staining characteristics of AK auto Ab. They also proved that main targets of AK auto Ab are tonofilaments and desmosomes in KC. AK auto Ab have a poor species specificity, but their tissue specificity is so strict that they can not even bind to transitional epithelium similar to epidermis. Research on the generation mechanism of AK auto Ab indicated that spleen cells of non-immunized mice can secrete AK auto Ab spontaneously. Biological function of AK auto Ab has been studied from various aspects by many scientists. A research by Hintner et al showed that IgG AK auto Ab opsonize insoluble aggregates of keratin intermediate filament (KIF). Another research reported that instantaneous deposition of AK auto Ab was observed on keratin bodies resulting from the apoptosis of KC, after these bodies dropped into the dermis. Thus, it is believed that AK auto Ab can accelerate the clearance of degenerated self-components produced in the body抯 metabolism by binding to them. In addition, research on the pathological significance of AK auto Ab indicated that there are relations between AK auto Ab and many diseases. In previous studies, we successfully established animal models with different serum titers of AK auto Ab. These models laid a foundation for the animal-based study of AK auto Ab. A later research showed that after autograft was embedded under the epidermis, instantaneous deposition of AK auto Ab could be locally observed on the regions with exposed keratins. After the formation of cyst, deposited AK auto Ab was gradually dissovled with the resolution of tissue reaction. We infer that AK auto Ab may provide early information for the following reactions that in the end lead to sealing exposed keratins, thereby playing an important role in immune response and homeostasis of the body. Under some pathological conditions, like cold injury, scald, contact dermatitis, AK auto Ab can actively participate in the -9...