Exposure to perflubron is associated with decreased Syk phosphorylation inhuman neutrophils

Liquid ventilation with perflubron is associated with reduced neutrophil re cruitment into the lung during acute injury. Perflubron also reduces chemot actic responses, the respiratory burst, and cytokine production in neutroph ils and in alveolar macrophages in vitro. In the current studies, the effec t of perflubron on neutrophil chemotaxis to formyl-Met-Leu-Phe (fMLP) and p hagocytosis of opsonized sheep erythrocytes (EA) correlated with decreased phosphorylation of Syk, an important intracellular second messenger in path ways regulating neutrophil functional responses. Brief (5 min) exposure of neutrophils to perflubron resulted in a dose-dependent reduction in chemota xis to fMLP and reduced phagocytosis of EA but no apparent morphological ch anges as seen by electron microscopy. Concurrently, there was a reduction i n both total cytosolic tyrosine phosphorylation and Syk phosphorylation. Bi nding studies indicated that this effect was neither a result of impaired l igand-receptor affinity nor a change in the number of fMLP receptors availa ble on the neutrophil surface. These results suggest that perflubron nonspe cifically affects cellular activation as measured by tyrosine phosphorylati on perhaps by interfering with transmembrane signal transduction.