PUB059 Role of Alveolar Macrophages' Molecular Antennas in the Pathogenesis of Lung Cancer

Abstract

The internal sources of alpha-emitting radionuclides originated from tobacco smoke or inhaled contaminated aerosol, induce the low-slow dose effects in pulmonary tissue. The health effects may not appear for years. The metabolic, ionic and enzyme properties of alveolar macrophages (AM), represent in situ biochemical, immunological and signaling processes. Apoptotic regulation is important for tissue remodeling. The study was performed in order to elucidate some of the mechanisms included in the pathogenesis of lung cancer. Bronchoalveolar lavage (BAL) was performed in a group of smokers whose average smoking exposure (pack-years) values were < 2, and patients with non-small cell lung cancer (NSCLC) > 40, as well as in the control group of nonsmokers. Differential cell counting and cytochemical analysis of the BAL specimens for intracellular iron content, lipids, glycogen, nonspecific esterases, and acid phosphatase (ACP) were performed by light microscopy. Apoptosis detection was performed by using the TUNEL in situ cytochemical method. Iron content in AM is gradually increasing in smokers, as well as in patients with NSCLC, (p<0.05) in comparison with non-smokers. There were no significant differences for ACP, nonspecific esterases, glycogen and lipid content in AM between the investigated groups. Apoptosis is gradually increasing in smokers and NSCLC group in comparison with nonsmokers. Apoptotic clearance of free apoptotic bodies by AM phagocytosis is increased in smokers in comparison with nonsmokers, but in the NSCLC group, AC is significantly decreased both, in comparison with nonsmokers, as well as control smokers (p<0.05). AM possess iron centers in their enzymes. The regulation of gene expression for ACP depends on iron. The binuclear iron center of ACP is included in the generation of reactive oxygen species. During the prolonged tissue injury, AM gather iron which can itself contribute to the process of cell damage, as an ionic part of molecular antennas (biomolecules, including enzymes with metal ion surrounded by biopolymer chains). Ferroptosis could be an iron-dependent form of non-apoptotic death of AM, without cell energy depletion. Alpha-emitting internal sources of radiation may trigger random and irregular tissue damage and repair. Oxygen diffusion limit increases for the population of proliferating cells. Their metabolic phenotype changes from glycolytic to lipogenic, with the further transformation of cells to the initiation of neoplastic lesion in the prolonged course. The changed biological properties of AM could be of importance as a utility for biological dosimetry purposes.