Halayko A J, Rector E, Stephens N L
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Am J Physiol. 1998 Jan;274(1):L17-25. doi: 10.1152/ajplung.1998.274.1.L17.
Growth and maturation state of airway smooth muscle cells (SMCs) are determinants of asthma pathophysiology. Heparin reduces airway SMC proliferation and arterial SMC replication and phenotypic modulation. Distinct arterial SMC subtypes, differing in heparin sensitivity, have been characterized. We assessed the cellular mechanisms underlying the growth and phenotype of heparin-treated canine tracheal myocytes in primary culture. Heparin reduced replication by 40%. Immunoblot assay of myosin, actin, and myosin light chain kinase revealed heparin had no effect on rapid spontaneous phenotypic modulation after the cells were plated. Heparin increased cellular protein and vimentin contents in confluent cultures, suggesting that it may induce hypertrophic growth. Cell cycle analysis revealed that heparin decreased serum-stimulated replicating myocyte number by 40%. Also, G2-M transit was 20% slower for the set of SMCs that proceeded past G1 in the presence of heparin. These data indicate that heparin does not inhibit airway SMC replication by blocking modulation from the contractile state. Moreover, airway smooth muscle is composed of distinct SMC populations differing in mitogen and antiproliferative mediator responsiveness. Identification of functionally divergent subgroups suggests that distinct sets of SMCs may contribute differentially to airway physiology and pathophysiology.
气道平滑肌细胞（SMC）的生长和成熟状态是哮喘病理生理学的决定因素。肝素可减少气道SMC增殖以及动脉SMC复制和表型调节。已鉴定出对肝素敏感性不同的不同动脉SMC亚型。我们评估了原代培养中肝素处理的犬气管肌细胞生长和表型的细胞机制。肝素使复制减少了40%。对肌球蛋白、肌动蛋白和肌球蛋白轻链激酶的免疫印迹分析显示，在细胞接种后，肝素对快速自发表型调节没有影响。肝素增加了汇合培养物中的细胞蛋白和波形蛋白含量，表明它可能诱导肥大生长。细胞周期分析显示，肝素使血清刺激的复制性肌细胞数量减少了40%。此外，在肝素存在的情况下，通过G1期的那组SMC的G2-M期过渡慢了20%。这些数据表明，肝素不是通过阻断从收缩状态的调节来抑制气道SMC复制。此外，气道平滑肌由对有丝分裂原和抗增殖介质反应性不同的不同SMC群体组成。功能不同亚组的鉴定表明，不同组的SMC可能对气道生理和病理生理学有不同的贡献。
