Actin is one of the most abundant of the constituents of the proteome. In its polymeric filamentous form, actin is a critical component of the cytoskeleton, so influencing cell shape and motility. It is viewed by the research community from several different perspectives. For example, cell biologists view actin as the major element in a complex suite of molecules that maintain cell form and mediate cellular motility responses to various stimuli, e.g., chemotaxis, covered in detail in other chapters of this book. Analytical biochemists take advantage of the cellular abundance and high conservation of structure of actin to use it as a “housekeeping” protein control for particular functional studies on other elements of the proteome. Immunopathologists and diagnostic serologists are interested in the propensity of actin to behave as an autoantigenic molecule, which it does in virtually just one disease, autoimmune hepatitis (AIH). This chapter is written from this third perspective. The chapter is introduced by a brief survey of immunity and autoimmunity, and the nature of the disease AIH in which F-actin functions as an autoantigen. The chapter examines anti-F-actin in terms of its origins and significance, and possible role in immune-mediated destruction of hepatocytes. Functional effects in vitro of anti-F-actin (delivered as Fabs of IgG) on actin motility are demonstrable using an actin-myosin system in a motility chamber.
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- Chretien-Leprince, P., Ballot, E., Andre, C., Olsson, N. O., Fabien, N., Escande, A., Oksman, F., Dubuquoi, S., Jego, S., Goetz, J., Chevaller, A., Sanmarco, M., Humbel, R. L. and Johanet, C. 2005. Diagnostic value of anti-F-actin antibodies in a French multi-center study. Ann. NY Acad. Sci. 1050, 266-273.CrossRefPubMedGoogle Scholar
- Cunningham, A. L., Mackay, I. R., Frazer, I. H., Brown, C., Pederson, J. S., Toh, B. -H., Tait, B. D. and Clarke, F. M. 1985. Antibody to G-actin in different categories of alcoholic liver disease: Quantification by an ELISA and significance for alcoholic cirrhosis. Clin. Immunol. Immunopathol. 34, 158-164.CrossRefPubMedGoogle Scholar
- Homberg, J.-C., Abuaf, N., Bernard, O., Alvarez, F., Khalil, S. H., Poupon, R., Darnis, F., Levy, F.-G., Grippon, P., Opolon, P., Bernuau, J., Benhamou, J.-P. and Alagille, D. 1987. Chronic active hepatitis with anti-liver/kidney microsome antibody Type 1: A second type of autoimmune hepatitis. Hepatology 7, 1333-1339.CrossRefPubMedGoogle Scholar
- Kurki, P. 1994. Cytoskeleton antibodies. In Autoimmune Hepatitis. M. Nishioka, G. Toda and M. Zeniya (Editors). Elsevier Science, Netherlands. pp. 185-198.Google Scholar
- Lang, K. S., Rechner, M., Junt, T., Navarini, A. A., Harris, N. L., Freigang, S., Odermatt, B., Conrad, C., Ittner, L. M., Bauer, S., Luther, S. A., Uematsu, S., Akira, S., Hengartner, H. and Zinkernagel, R. M. 2005. Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease. Nat. Med. 11, 138-145.CrossRefPubMedGoogle Scholar
- Ma, Y., Bogdanos, P., Hussein, M. J., Underhill, J., Bansal, S., Longhi, M. S., Cheeseman, P., Miele-Vergani, G. and Vergani, D. 2006. Polyclonal T-cell responses to cytochrome P450 IID2 are associated with disease activity in autoimmune hepatitis type 2. Gastroenterology 130, 868-882.CrossRefPubMedGoogle Scholar
- Rizetto, M., Swana, G. and Doniach, D. 1973. Microsomal antibodies in active chronic hepatitis and other disorders. Clin. Exp. Immunol. 15, 331-344.Google Scholar
- Vergani, D., Alvarez, F., Bianchi, F. B., Cancado, E. L. R., Mackay, I. R., Manns, M. P., Nishioka, M. and Penner, E. 2004. Autoimmune serology: A consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group. J. Hepatol. 41, 677-683.CrossRefPubMedGoogle Scholar