Asbestos-related increase in pulmonary levels of vasoactive intestinal peptide (VIP)

Abstract

Vasoactive intestinal peptide (VIP), leucine-enkephalin (Leu-Enk), dynorphin (Dyn), neurotensin (NT) and substance P (SP) were measured by radioimmunoassay in lung and bronchoalveolar lavage (BAL) fluids of sham operated control rats and rats exposed to asbestos (5 and 10 mg, single intratracheal injections) for 3 and 6 months. Among these peptides, VIP, Leu-Enk and Dyn were the most abundant with 6 to 25 pmoles per g of lung tissue as compared with 0.95 to 1.2 pmoles per g for the other neuropeptides. In the presence of asbestos, VIP levels were selectively increased up to 2.7 times in lung tissue and 4.3 times in BAL fluids. On high pressure liquid chromatography (HPLC), the immunoreactive VIP coeluted with synthetic VIP. It is concluded that this selective increase may be involved in the pathogenesis of asbestos-related diseases. Exposure to asbestos causes chronic inflammatory reactions in the lung which may lead to fibrosis (1) and increase the incidence of pleuropulmonary cancers (2). Little is known concerning the biochemical changes responsible for the deleterious effects of asbestos on pulmonary functions. Previous studies have documented the vast complexity and diversity of lung biochemistry including its ability to metabolize lipids, inactive certain enzymes and produce physiologically active amines (3–6). Recently, the lung has been recognized as an important source of peptidergic substances. VIP and SP were reported to be localized in nerve terminals of the main airways and in axons of the parasympathetic conducts (7–11). Other neuropeptides including bombesin (12, 13), calcitonin (13, 14) and Leu-Enk (13) were also detected in the lung. However, these latter peptides were mainly confined to diffuse granule-containing cells also known as APUD cells (amine precursor uptake and decarboxylation cells) (15). The role of these neuropeptides in normal lung function and in pulmonary diseases is unknown. However, it has recently been demonstrated that APUD cells proliferate in the rat lung following asbestos inhalation (16) and lung exposure to carcinogens (17, 18). In addition, Moody et al. (19) and Sorenson et al. (20) have observed high levels of bombesin in human cell lines derived from small-cell lung carcinoma. It was then of particular interest to verify if lung exposure to asbestos can induce some changes in the levels of various neuropeptides. In the present study, we report that VIP is significantly increased in the lungs and BAL fluids of rats exposed to asbestos while no significant change in the levels of Leu-Enk, Dyn, NT and SP is observed.