AIRWAY SMOOTH-MUSCLE CONTRACTILE, REGULATORY AND CYTOSKELETAL PROTEINEXPRESSION IN HEALTH AND DISEASE

The major part of research dealing with the biophysical and biochemica l properties of airway smooth muscle is based on the assumption that t he cells constituting the tissue are homogenous. For striated muscle t his has been shown untenable. In recent years almost every property of vascular smooth muscle has been also demonstrated re, be heterogeneou s. This realization has been late in arriving on the airway smooth mus cle research scene. Our own studies have shown that mechanical propert ies are, in quantitative terms, heterogeneously distributed down the a irways and that contractility, for example, in extrapulmonary and intr apulmonary airways differs markedly. Another indication of heterogenei ty is derived from studies of the biochemical properties of airway smo oth muscle cells (ASMCs) in culture. Dramatic changes in phenotype exp ression were found with days in culture. Just after isolation from the tissue; the cells were of contractile type and contained mature isofo rms of contractile, regulatory and cytoskeletal proteins. After the fo urth day in culture the cellular phenotype changed such that contracti le filaments diminished rapidly with smooth muscle isoforms being repl aced by non-muscle isoforms. The cell assumed secretory or synthetic p roperties and commenced proliferating rapidly. It is possible that sim ilar changes in phenotype could occur in vivo in cells undergoing hype rtrophy or hyperplasia. Thus, a thickened medial layer of the type see n in the walls of airways from asthmatic airways is not necessarily on e endowed with increased contractility and, in fact, the latter may be subnormal. Finally, using the so-called motility assay, we studied th e velocity of translation of actin filaments by myosin molecules obtai ned from antigen-sensitized and control airway smooth muscle. We found no change in maximum velocity of actin translation. This was under co nditions where the myosin light chain (MLC) was fully phosyhorylated. However, in these tissues we found heterogeneity in myosin light chain kinase (MLCK) content which, we inferred, accounted for the differenc e in shortening velocity between control and sensitized muscle strips in vitro. (C) 1998 Elsevier Science Inc. All rights reserved.