NO-dependent regulation of lectin- and menadione-induced H2O2 production by cells from pleural effusions of lung cancer patients and by immune cells.

Molecular mechanisms of interplay between reactive oxygen (superoxide, hydroxyl radical, H2O2 etc.) and nitrogen (nitric oxide - NO, ONOO-, NO2-, NO3- etc.) forms are proposed to be of key importance for cell and tumor biology. Considering NO as a signal molecule we have studied the impact of NO release on processes of generation of H2O2 in different experimental systems including pleural effusions (PE) of lung cancer patients, human polymorphonuclear leukocytes (PMNs), and rat thymocytes. It was found that PE of lung cancer patients contain a high level of [NO2-+NO3-], i.e. 43.4 25.6 microM (n=15), and PE cells could effectively generate H2O2 in response to lectins from Viscum album (VAA), Phaseolus vulgaris (PHA), and Pisum sativum (PSA) as well as to menadione. A positive correlation between the [NO2-+NO3-] concentration and menadione-induced H2O2 generation (r=0.1964) was found, whereas the [NO2-+NO3-] concentration and lectin-induced H2O2 generation (PHA, r=-0.4099; PSA, r=-0.3949; VAA, r=-0.3225) were negatively correlated. Notably, an increase of H2O2 generation by PE cells was determined in the range of 20-35 microM [NO2-+NO3-]. When PMNs and rat thymocytes were treated with a donor of NO (sodium nitroprusside), the release of H2O2 in response to lectins or menadione was decreased in a dose-dependent manner. The end products of NO biochemistry, assayed as KNO2 and KNO3, were not able to affect significantly the H2O2 generation processes. In conclusion, the data indicate that the potential for triggered H2O2-generation of cells is modulated markedly by the presence of NO or derived reaction compounds. This relation may play an important role in the pathogenesis of PE malignancies with potential relevance for therapeutic strategies.