The lung and other organs are comprised of both cellular and extracellular compartments. Interaction of these components modulates physiological function at the organ, cellular, and subcellular levels. Extracellular components in the gas-exchange region of the lung include both noncellular interstitium and basement membranes. Connective tissue elements of the interstitium in part determine ventilatory function by contributions to tissue compliance and to resistance of the diffusion barrier. The basement membrane underlies cells of both the alveolar epithelium and the capillary endothelium; basement membrane components exert biological effects on adjacent cells through receptor-mediated interactions. This review emphasizes current knowledge concerning the composition and biological activity of extracellular matrix in the alveolar region of the lung. Matrix synthesis and turnover are also considered. Directions for future research are suggested in the context of current knowledge of the lung and other model systems.

Cultured alveolar epithelial cells exhibit gap junction intercellular communication (GJIC) and express regulated levels of connexin (Cx) 43 mRNA and protein. Newly synthesized radiolabeled Cx43 protein equilibrates with phosphorylated Cx43 isoforms; these species assemble to form both connexons and functional gap junction plaques. The saponin 18α-glycyrrhetinic acid (GA) rapidly and reversibly blocks GJIC at low concentrations (5 μM). Extended exposure to 18α-GA at higher concentrations causes inhibition of GJIC and time- and dose-dependent reductions in both Cx43 protein and mRNA expression. The latter toxic effects are paralleled by disassembly of gap junction plaques and are reversed less readily than acute effects on GJIC. These observations demonstrate 18α-GA-sensitive regulation of intercellular communication in epithelial cells from the mammalian lung and suggest a role for Cx43 expression and phosphorylation in acute and chronic regulation of GJIC between alveolar epithelial cells.

In many species, partial resection of the lung leads to rapid compensatory growth of the remaining tissue to restore normal lung mass and function. The response to partial pneumonectomy is closely controlled; both its rate and nature are subject to hormonal modulation. Physical factors, particularly distortion of the lung by altered inflation, are likely involved in regulation of the response, although the details of the regulatory mechanisms are not understood. In a number of tissues including the lung, application of external physical force leads to both acute and long-term changes in metabolism. In some cases these include cell growth and division, along with increased production of extracellular matrix components. Similar responses have been described after application of stress to isolated cells in culture. Independent lines of investigation have defined dramatic influences of cell shape on growth, differentiation, and metabolism, but stress-strain relationships at the cellular or subcellular levels are poorly defined. The mechanisms by which changes in cell shape are transduced to intracellular signals likely depend on receptor-mediated interactions with the cytoskeleton, but strain-associated transduction pathways may involve stretch-sensitive ion channels, G protein-dependent reactions, the action of locally produced autocrine or paracrine factors, or a combination of these factors. These observations suggest a general model of the response to pneumonectomy that may be used to formulate specific hypotheses as a basis for future investigations. This approach will provide insight into the mechanisms by which physical forces influence growth and metabolism in the lung and other tissues.