Polyamines in the lung: polyamine uptake and polyamine-linked pathologicalor toxicological conditions

The natural polyamines putrescine,: cadaverine, spermidine, and spermine ar e found in all cells. These (poly)cations exert interactions with anions, e .g., DNA and RNA. This feature represents their best-known direct physiolog ical role in cellular functions: cell growth, division, and differentiation . The lung and, more specifically, alveolar epithelial cells appear to be e ndowed with a much higher polyamine uptake system than any other major orga n. In the-lung, the active accumulation of natural polyamines in the epithe lium has-been studied in various mammalian species including rat, hamster, rabbit, and human. The kinetic parameters (Michaelis-Menten constant and ma ximal uptake) of the uptake system are the same order of magnitude regardle ss of the polyamine or species studied and the in vitro system used. Also, other pulmonary cells accumulate polyamines-but never to the same extent as the epithelium. Although different uptake:systems exist for putrescine, sp ermidine, and spermine in the lung, neither the nature of the carrier prote in nor the reason for its existence is known. Some pulmonary toxicological and/or pathological conditions have been related to polyamine metabolism an d/or polyamine content in the lung. Polyamines possess an important intrins ic toxicity. From in vitro studies with nonpulmonary cells, it has been sho wn that spermidine and spermine can be metabolized to hydrogen peroxide, am monium, and acrolein, which can all cause cellular toxicity. In hyperoxia o r after ozone exposure, the increased polyamine synthesis and polyamine con tent of the rat lung is correlated with survival of the animals. Pulmonary hypertension induced by monocrotaline or hypoxia has also been linked to th e increased polyamine metabolism and polyamine content of the lung. In a sm all number of studies, it has been shown that polyamines can contribute to the suppression of immunologic reactions in the lung.