CHARACTERIZATION OF MOLECULAR DETERMINANTS OF SMOOTH-MUSCLE CELL HETEROGENEITY

Broad diversity in contractile and pharmacological properties of diffe rent smooth muscles is well recognized. Differences in proliferative c apacity, electrophysiology, phenotypic marker protein content, matrix synthesis, and expression of cell-specific transcription factors betwe en individual smooth muscle cells (SMCs) have also been reported. Prec ise developmental and molecular mechanisms underlying heterogeneity ar e not known; however, their elucidation is the thrust of much current research involving vascular smooth muscle. In contrast, limited studie s of heterogeneity of subtypes of airway SMCs are available. In this r eport, we review molecular aspects of differentiation that may determi ne phenotypic heterogeneity of SMCs and also present data from our own studies characterizing heterogeneity in the proliferative capacity an d marker protein content of airway SMCs. Using flow cytometry, cell cy cle transit was monitored for cultured canine tracheal SMCs. Only 70% of arrested cells responded and traversed the cell cycle when stimulat ed with 10% fetal bovine serum. Furthermore, heparin inhibited 40% of serum-responsive cells from entering the cell cycle, suggesting that b oth serum- and heparin-sensitive and -insensitive airway SMCs exist. F low cytometric analysis of contractile protein and DNA content in fres hly dissociated canine tracheal SMCs revealed that diploid (similar to 87%) and tetraploid (similar to 13%) populations exist. Clusters of S MCs having ''high'' or ''low'' smooth muscle myosin or alpha-actin con tent were also discerned, indicating that distinct subtypes of SMCs ex ist in mature airways. Diversity of SMCs may be a critical factor dete rmining specific responses of smooth muscles to a number of physiologi cal or pathophysiological stimuli that may include, for example, infla mmatory mediators in asthmatic airways.