Methods and achievements in experimental pathology最新文献

The cytoskeletal proteins, actin, myosin, tubulin, dynein, and their associated proteins, are discussed selectively with regards to their biochemical and structural properties. Particular emphasis is placed on the comparison of non-muscle proteins to their muscle counterparts, and on the various mechanisms for regulating actin polymerization, actin-myosin interaction, and tubulin polymerization. This review as well as the bibliography accompanying it is selective. An attempt is made to stress the most recent findings and to emphasize those areas which appear to hold the greatest promise for future research.

Smooth muscle antoantibodies are found in high titre in some patients with chronic active hepatitis, and in lower titres in a number of other liver diseases and certain viral infections. They are directed at contractile proteins of the actomyosin group, and anti-actin activity appears to predominate. Whether occurring in disease affecting the liver or in other conditions, smooth muscle antibody production is thought to be stimulated when contractile proteins of non-muscle cells become immunogenic as a result of changes induced in the cells by viral infection or by other unknown causes of derangement of cytoskeletal structure.

Cytoskeletal proteins are demonstrated in the interstitial cells of the lungs. These proteins appear in the cytoplasm as bundles of microfilaments, the individual filaments measuring 40--80 A in diameter. The presence of actin and myosin in these cells is demonstrated by immunofluorescence. Antiactin antibodies (AAA) obtained from patients with chronic aggressive hepatitis, as well as AAA and antimyosin antibodies prepared in the rabbit, are used. The major difference between the cytoskeletal proteins of interstitial cells and other cells of the alveolar tissue (type II epithelium, pericytes, and near the junctional complexes of endothelial cells) is that the microfilaments within the interstitial cells are organized into bundles forming tiny intracytoplasmic 'muscles'. Furthermore, they appear to be much more abundant and seem to anchor the cell on the alveolar basement membrane by hemidesmosome-like structures. These peculiar cytological features provide these cells with an important functional capacity. Being located in the 'pillars' which cross the capillary space, the contraction of interstitial cells may modify the alveolocapillary configuration in some circumstances. The physiological importance of such an 'active' alveolar motility is to provide the lung with a mechanism of autoregulation of the ventilation/perfusion (V/Q) ratio at alveolar level.

Several lines of evidence point to the existence of unpolymerised actin in non-muscle cells. Ultrastructural examination reveals both a variety of actin filament bundles and actin in a controversial organisational state. Arguments are cited that this material, which at least in part is found close to the plasma membrane, represents unpolymerised actin rather than a random array of single actin filaments. The rearrangement of actin filament bundles during the cell cycle, and in response to experimental manipulation, suggests a turnover of filaments by a polymerisation-depolymerisation cycle. Extracts made from non-muscle cells under conditions where muscle actin would polymerise still contain appreciable fractions of monomeric actin. Studies on purified polymerisation-resistant actin from a variety of sources reveal the presence of a small protein which binds specifically to actin and prevents polymerisation. In the last section of the article, we expand the idea that this auxiliary protein is a central control element in the regulated exchange between non-polymerised and polymerised actin in vivo.