Perflubron Emulsion Does Not Cause Neutrophil (PMN) Activation In- Vivo.

Abstract

Earlier, we reported that in-vitro incubation of blood for ten minutes with the perfluorocarbon (PFC) emulsion Fluosol increased leukocyte activation as determined by adhesion to nylon fiber. In this study, we examined if in-vivo treatment with these PFC emulsions affected the expression of the leukocyte adhesion protein CD11b (primarily found on PMNs) and the generation of leukocyte-derived reactive oxygen species (ROS, oxygen free radicals). Rats were anesthetized and catheterized. Three groups were studied: 1) a phosphate buffered saline (PBS) control group (n=6), 2) a group treated with Fluosol emulsion (1.08g PFC/kg, n=6) and 3) a group treated with perflubron emulsion (1.08g PFC/kg, n=6). Blood samples were taken before and 10, 20, 40 and 60 minutes after treatment for hematology and analysis of PMN CD11b expression and ROS production using flow cytometry. We found that Fluosol caused significant increases in both neutrophil surface expression of CD11b and ROS generation (p<0.05, ANOVA). In the Fluosol group, the peak responses in PMN CD11b expression and ROS production were observed ten minutes after treatment. In contrast, treatment with perflubron emulsion did not cause a significant increase in CD11b expression nor an increase in ROS production at any time after treatment. These findings suggest that Fluosol causes a transient PMN activation in-vivo. The activation of circulating PMNs, in-vivo, is sufficient to significantly enhance oxygen derived free radical production. The lack of a PMN response to perflubron emulsion in-vivo suggests that this agent is not likely to induce a leukocyte-mediated inflammatory response.