The Importance of Epithelial Uptake Systems in Lung Toxicity

Abstract

The discovery that the herbicide paraquat was selectively accumulated by the lung, both in vivo and in vitro, in comparison with other tissues, provided an explanation for its selective toxicity to the lung. This uptake process is energy dependent and obeys saturation kinetics. A characterization ofthe process led to the identification of endogenous chemicals that are the natural substrates for the system. Among these are a series of diamines and polyamines, as well as the diaminodisulfide cystamine. It appears that paraquat, because of specific structural similarities to these endogenous polyamines, is mistakenly accumulated by the lung. This uptake process is specifically located in the alveolar Type II cell, the Clara cell, and probably the alveolar Type I cell.With the development of knowledge of the structural requirements of chemicals to be accumulated by this system, it is possible to predict which chemicals will be accumulated by the lung or design molecules that are targeted to the alveolar epithelial and Clara cells.In the wider perspective, this polyamine uptake system has been found on a number of cancerous cells or tissues. With the knowledge of the uptake system in the lung, it should be possible to design drugs that will be specifically concentrated in cells that possess this system. IntroductionBecause the lung is responsible for all gas exchange necessary for oxidative metabolism, it is inevitably exposed to toxic gases, vapors, and particles (if small enough) present in the atmosphere. The respiratory function of the lung requires a large surface area (in man, about the size of a tennis court) that, on the air side, is covered by epithelial cells intimately associated with an extensive capillary network. Apart from inhalation, the lung is also exposed to toxic compounds that have been absorbed into the bloodstream or are in the form of metabolites, formed either in the lung or in extrapulmonary tissue.In order to meet its respiratory function, the lung requires numerous cell types. More than 40 cell types have been identified in the lung (1); these are required to provide the diverse architecture associated with cartilage, smooth muscle, connective tissue, submucosal glands, the vascular system, and the respiratory unit (alveoli)

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Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

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