title: Lung surfactant gelation induced by epithelial cells exposed to air pollution or oxidative stress.
abstract: Lung surfactant lowers surface tension and adjusts interfacial rheology to facilitate breathing. A novel instrument, the interfacial stress rheometer (ISR), uses an oscillating magnetic needle to measure the shear viscosity and elasticity of a surfactant monolayer at the air-water interface. The ISR reveals that calf lung surfactant, Infasurf, exhibits remarkable fluidity, even when exposed to air pollution residual oil fly ash (ROFA), hydrogen peroxide (H2O2), or conditioned media from resting A549 alveolar epithelial cells (AEC). However, when Infasurf is exposed to a subphase of the soluble fraction of ROFA- or H2O2-treated AEC conditioned media, there is a prominent increase in surfactant elasticity and viscosity, representing two-dimensional gelation. Surfactant gelation is decreased when ROFA-AEC are pretreated with inhibitors of cellular reactive oxygen species (ROS), or with a mitochondrial anion channel inhibitor, as well as when A549-rho0 cells that lack mitochondrial DNA and functional electron transport are investigated. These results implicate both mitochondrial and nonmitochondrial ROS generation in ROFA-AEC-induced surfactant gelation. A549 cells treated with H2O2 demonstrate a dose-dependent increase in lung surfactant gelation. The ISR is a unique and sensitive instrument to characterize surfactant gelation induced by oxidatively stressed AEC.
authors.affiliation: Department of Chemical Engineering, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305-5236, USA.
authors.forename: Jay W
authors.initials: JW
authors.lastname: Anseth
authors.forename: An J
authors.initials: AJ
authors.lastname: Goffin
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Fuller
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ghio
authors.forename: Peter N
authors.initials: PN
authors.lastname: Kao
authors.forename: Daya
authors.initials: D
authors.lastname: Upadhyay
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001688:Biological Products / Q000737:chemistry; D002417:Cattle; D002460:Cell Line; D004548:Elasticity; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005782:Gels; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007501:Iron / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012212:Rheology / Q000295:instrumentation / Q000379:methods; D014783:Viscosity
chemical_list: D000393:Air Pollutants; D001688:Biological Products; D005782:Gels; D011663:Pulmonary Surfactants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D007501:Iron; C117342:calfactant