Oxidants, nitrosants, and the lung

The respiratory tract is subjected to a variety of environmental stresses, including oxidizing gases, particulates, and airborne microorganisms, that together, may injure structural and functional lung components and thereby jeopardize the primary lung function of gas exchange. To cope with such var ious environmental threats, the lung has developed elaborate defense mechan isms that include inflammatory-immune pathways as well as several antioxida nt systems. These defense systems operate largely in extracellular spaces, thus protecting underlying bronchial and alveolar epithelial cells from inj ury, although these cells themselves are also active participants in such ( inflammatory) defense mechanisms. Although potentially harmful, oxidants ar e increasingly recognized as pathophysiologic mediators produced primarily by inflammatory-immune cells as a host defense mechanism, but also by vario us other cell types as an intracellular mediator in various cell responses, thus affecting inflammatory-immune processes or inducing resistance. The m olecular mechanisms and signaling pathways involved in such processes are t he focus of much current investigation. Nitric oxide, a messenger molecule produced by many lung cell types, also modulates oxidant-mediated processes , thereby giving rise to a new family of reactive nitrogen species ("nitros ants") with potentially unique signaling properties. The complex role of ox idants and nitrosants in various pathophysiologic processes in the lung hav e confounded the design of therapeutic approaches with antioxidant substrat es. This review discusses current knowledge regarding extracellular antioxi dant defenses in the lung, and oxidant/nitrosant mechanisms operating under inflammatory-immune conditions and their potential contribution to common lung diseases. Finally, some recent developments in antioxidant therapeutic strategies are discussed. (C) 2000 by Excerpta Medica, Inc.