AIRWAY SMOOTH-MUSCLE CELL-PROLIFERATION - CHARACTERIZATION OF SUBPOPULATIONS BY SENSITIVITY TO HEPARIN INHIBITION

Growth and maturation state of airway smooth muscle cells (SMCs) are d eterminants of asthma pathophysiology. Heparin reduces airway SMC prol iferation and arterial SMC replication and phenotypic modulation. Dist inct arterial SMC subtypes, differing in heparin sensitivity, have bee n characterized. We assessed the cellular mechanisms underlying the gr owth and phenotype of heparin-treated canine tracheal myocytes in prim ary culture. Heparin reduced replication by 40%. Immunoblot assay of m yosin, actin, and myosin Light chain kinase revealed heparin had no ef fect on rapid spontaneous phenotypic modulation after the cells were p lated. Heparin increased cellular protein and vimentin contents in con fluent cultures, suggesting that it may induce hypertrophic growth. Ce ll cycle analysis revealed that heparin decreased serum-stimulated rep licating myocyte number by 40%. Also, G(2)-M transit was 20% slower fo r the set of SMCs that proceeded past G(1) in the presence of heparin. These data indicate that heparin does not inhibit airway SMC replicat ion by blocking modulation from the contractile state. Moreover, airwa y smooth muscle is composed of distinct SMC populations differing in m itogen and antiproliferative mediator responsiveness. Identification o f functionally divergent subgroups suggests that distinct sets of SMCs may contribute differentially to airway physiology and pathophysiolog y.