Heterogeneity of airway smooth muscle at tissue and cellular levels

Abstract

Heterogeneity of smooth muscle behavior is rapidly emerging as an important phenomenon. However, it is only recently that investigators have begun to explore its physiological and pathogenic importance. Stenmark's group recently reported the existence of four subpopulations of smooth muscle cells in pulmonary artery, and noted that only a specific group of cells was likely responsible for the hyperplasia of smooth muscle in the hypertensive artery. Our studies reported here were focused on determining whether heterogeneity of contractile properties existed in airway smooth muscle cells. Firstly, mechanical properties of muscle strips, free of cartilage and epithelium, were compared among the different generations of canine airway from trachea down to bronchial generation 6. Two distinct groups of smooth muscle were detected from these airways: (i) an extrapulmonary group, consisting of muscle strips from the trachea, and bronchial generation 1 and 2, characterized by higher maximum shortening capacity (delta Lmax) and zero-load velocity (V0) of shortening; (ii) an intrapulmonary group, containing bronchi from generation 3 to 6, with lower delta Lmax and V0. This led to the implication that smooth muscles from these two groups consisted of different types of cells. Secondly, single smooth muscle cells were isolated from trachea and bronchus (from generation 3 to 6) enzymatically, and the unloaded shortening capacity of fresh isolated cells was measured employing electrical field stimulation at room temperature. Two types of cells were identified from these preparations based on the length of muscle cells: type I, with a mean length of 110 +/- 3 microns (SE), predominated in trachea (up to 84%); type II, with a mean length of 200 +/- 9 microns (SE), accounted for 58% in bronchus. The mechanical properties of these two types of cells were also different. Type I cells shortened by 28% of their original lengths in response to maximal stimulation, while most type II cells (90% of total type II cells) shortened 16% (type IIA), and the remainder shortened 58% (type IIB). Because of the paucity of information about the orientation and arrangement of these different types of smooth muscle cells in the airway tree, it is difficult to apply these data directly for interpretation of differences in mechanical properties of smooth muscle cells obtained from strips from extrapulmonary and intrapulmonary airways. Existence of great numbers of cells with lower shortening capacity in intrapulmonary airways may be the major factor responsible for lower mechanical performance of these airway smooth muscle strips. The relatively lower mechanical performance of intrapulmonary airway smooth muscle may be of importance in preventing excessive narrowing of these airways during muscle contraction and optimizing airflow.