Influence of cationic local anesthetics on the metabolism and ultrastructure of human alveolar macrophages

Abstract

The concentrations of cationic local anesthetics present in effluents from subsegmental bronchoscopic lavage were determined. Subsequently, the effect of these agents on lavaged human AM was evaluated in vitro. The results indicate that concentrations of LDC that may alter human AM function are present in effluents during routine subsegmental bronchopulmonary lavage. LDC and TRC in a dose-dependent fashion rapidly inhibited oxygen consumption and superoxide anion (O-2.) release by unstimulated human AM or AM stimulated by bacteria or the membrane-active chemical PMA. Concentrations of 2 mM TRC or 16 mM LDC reduced O2 consumption and O-2. release by unstimulated AM by more than 70% and blocked the usual spurt in O2 uptake and O-2. release observed for stimulated AM. This inhibition was not due to cytotoxicity, since washing n a balanced salt solution restored the metabolic function of treated AM. TRC or LDC also had effects on the morphology of washed human AM, causing rounding of the cell surface (scanning electron microscopy). In summary, the findings show that anesthetic agents routinely present in lavage effluents have the capacity to alter the function and structure of human AM. Although the effect must be considered in the design and interpretation of studies using AM obtained by bronchopulmonary lavage, the cationic anesthetics may also prove to be valuable agents for evaluating cell membrane-related events of human AM.