Phagocytic activation of human neutrophils by the detergent component of fluosol.
Fluosol (Alpha Therapeutic Corporation, Los Angeles, CA) an emulsion of perfluorocarbons with a high oxygen-carrying capacity, was approved as an adjunct to alleviate myocardial ischemia during coronary angioplasty. This drug also significantly enhances myocardial salvage presumably related to an action on the neutrophil. The mechanism by which fluosol and its individual components, including the detergent Pluronic F-68, affected neutrophil function was examined. During the incubation of neutrophils with fluosol, a rapid stimulation of superoxide anion production and degranulation which progressively increased over a 30-minute period was detected. Neutrophils incubated with only Pluronic F-68 produced similar amounts of superoxide anion. Cytochalasin B, an inhibitor of phagocytosis, significantly inhibited this superoxide anion generation. As shown previously, neutrophils incubated with fluosol for 30 minutes and then subsequently stimulated manifested a reduction in lysozyme release as compared with untreated cells. Results of an electron microscopic examination confirmed the cellular uptake of the fluosol within phagocytic vacuoles. Neutrophil viability determined by trypan blue was unaffected after fluosol treatment. These observations show that the fluosol emulsion, primarily through micelles formed by the detergent Pluronic F-68, activates human neutrophils by serving as a phagocytic stimulus, which produces a cell refractory to subsequent stimulation.
Ingram
D A
DA
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0111.
Forman
M B
MB
Murray
J J
JJ
D001802:Blood Substitutes; D003571:Cytochalasin B / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology*; D005466:Fluorocarbons / Q000494:pharmacology*; D005609:Free Radicals; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008854:Microscopy, Electron; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D011060:Poloxalene / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D001802:Blood Substitutes; D003902:Detergents; D005466:Fluorocarbons; D005609:Free Radicals; D007546:Isoquinolines; D013481:Superoxides; D003571:Cytochalasin B; C050455:fluosol; C065081:perfluoro-N-methyldecahydroisoquinoline; D011060:Poloxalene; D009113:Muramidase