Pulmonary Surfactant Interactions With Respirable Particles

This review summarizes three sets of ongoing studies which we are performing in collaboration with a number of researchers associated with the Dept. of Interior - Generic Mineral Technology Center for the Study of Respirable Dusts, concerning surfactant-particle interactions studied using this surrogate surfactant. These topics are: (A) the suppression of mineral particle cytotoxic potential by DPL adsorption and the persistence of this effect under conditions of enzymatic digestion; (B) surfactant suppression of organic particle cytotoxicity by DPL adsorption and the effect on subsequent expression of genotoxic potential; (C) potential effects of surfactant on heterogeneous structured complex respirable particles. The references list some of our reports which can provide additional information on these studies. Further, those reports provide references to the literature of the field and to the works of others on these topics. Deep lung airspaces, the pulmonary alveoli and respiratory bronchioles, are coated with a hypophase which is rich in surfactant biomolecules secreted by the alveolar type II epithelial cells. The surfactant is known to be critical to maintaining stable low surface tensions on the inner surfaces of the alveoli by forming a surfactant layer on the airliquid interface of the alveolar hypophase. Upon deposition in the acinar regions of the lung a respired particle's initial contact will be with this surfactant coating over pulmonary tissue. A primary component of this surfactant is the phospholipid diacyl glycerophosphorylcholine, commonly called lecithin. A surface layer of dipalmitoly lecithin on saline will act much as full pulmonary surfactant in decreasing surface tension and producing a hysteresis in surface tension behavior with surface area. We have used dipalmitoyl glycerophosphorylcholine, or dipalmitoyl lecithin (DPL), a major component of that surfactant, dispersed in physiologic saline as a surrogate for studying interactions of both mineral and organic respirable particles with pulmonary surfactant and consequent effects on particle toxic behavior. A. DUST CYTOTOXICITY AND LECITHIN SURFACTANT ADSORPTION Respirable quartz and kaolin clay particles are found to be comparably cytotoxic in a number of in vitro bioassays including lavaged rat pulmonary macrophage release of cytosolic and lysosomal enzymes, and red blood cell hemolysis as a measure of dust membranolytic potential. These direct and prompt cytotoxic activities do not account for the distinctly greater potential for quartz to induce pulmonary disease. When respirable quartz and kaolin are incubated with a dispersion of DPL in saline at 37C it is found that the prompt cytotoxicity of both dusts is fully suppressed as measured in vitro by pulmonary macrophage release of lactate dehydrogenase, beta-N-