Mast cell-derived mediators and their role in cell-to-cell interactions in the lung

Mast cells produce a variety of enzymes and vasoactive, chemotactic, and bronchoconstrictor substances in response to nonimmunologic as well as immunologic stimuli. These mast cell-derived mediators may act on airway smooth muscle, submucosal glands, epithelial cells, circulating blood cells, vascular cells, and other cell types. The secretory profile of a mast cell appears to depend on the specific stimulus applied. In addition, different populations of mast cells exist, and distinct enzymatic pathways may predominate in different cell types. The effect of mast cell-derived mediators on the various target cells may be direct or indirect. For example, mediators released by immunologic challenge of sensitized lung fragments or by nonimmunologic challenge of canine mastocytoma cells stimulate the transport of ions and water across the tracheal epithelium. This effect, however, is indirect, is blocked by indomethacin, and therefore appears to be dependent upon an intact cyclooxygenase pathway in the tracheal epithelium. Canine mastocytoma cells resemble normal mast cells in dog lung and skin, and can be propagated to provide a continuous source of large numbers of pure, identical mast cells for biochemical and physiologic studies. Studies of these cells and their inflammatory mediators will increase our understanding of the complex series of cell-to-cell interactions which are responsible for the pathophysiologic manifestations of obstructive lung disease.