Substance P receptor-dependent responses of leukocytes in pulmonary inflammation

Pulmonary immunologic responses may be mediated and modulated in part by neuropeptides released from the endings of nerve fibers that innervate the airways. Bronchoconstriction, mucosal edema, and increased airway secretions may be mediated by multiple locally generated neuropeptides. The neuropeptides affect directly and indirectly through other mediators the functions of endothelial cells, smooth muscle cells, blood vessels, and leukocytes. The high content of diverse potent neuropeptides in the ganglionated plexuses close to pulmonary smooth muscle bundles, along blood vessels, and in neural projections into the bronchial epithelium and regions containing acini of mucus glands provide tissue concentrations well within the range required to attain such biologic effects. The airway responses mediated principally by neuropeptides exhibit unique mechanisms of specificity attributable to the selective distribution of each neuropeptide in a distinct subset of nerve fibers that react differently to each stimulus and to the target cell specificity of the neuropeptides. At physiologically relevant in vitro concentrations, many of the neuropeptides have different effects on mast cells, basophils, monocytes, and lymphocytes. The direct actions of substance P (SP) and the capacity to initiate and modulate leukocyte responses are described in relation to the physiologic and pathopharmacologic consequences of pulmonary nerve stimulation. Selected cellular and molecular characteristics of the interactions of SP with mast cells, basophils, lymphocytes, endothelial cells, and smooth muscle cells also will be presented in order to define the functionally critical properties of receptors for the neuropeptide and to expose possible means of specifically modifying the interactions.