Raft localization of Type I Fcε receptor and degranulation of RBL-2H3 cells exposed to decavanadate, a structural model for V2O5

Abstract

Vanadium oxides (VOs) have been identified as low molecular weight sensitizing agents associated with occupational asthma and compromised pulmonary immunocompetence. Symptoms of adult onset asthma result, in part, from increased signal transduction by Type I Fcε receptors (FcεRI) leading to release of vasoactive compounds including histamine from mast cells. Exposure to (VOs) typically occurs in the form of particles which are insoluble. Upon contact with water or biological fluids, (VOs) form a series of soluble oxoanions, one of which is decavanadate, V₁₀O₂₈⁶⁻ abbreviated V₁₀, which is structurally related to a common vanadium oxide, that is vanadium pentoxide, V₂O₅. Here we investigate whether V₁₀ may be initiating plasma membrane events associated with activation of FcεRI signal transduction. We show that exposure of RBL-2H3 cells to V₁₀ causes a concentration-dependent increase in degranulation of RBL-2H3 and, in addition, an increase in plasma membrane lipid packing as measured by the fluorescent probe, di-4-ANEPPDHQ. V₁₀ also increases FcεRI accumulation in low-density membrane fragments, i.e., lipid rafts, which may facilitate FcεRI signaling. To determine whether V₁₀ effects on plasma membrane lipid packing were similarly observed in Langmuir monolayers formed from dipalmitoylphosphatidylcholine (DPPC), the extent of lipid packing in the presence and absence of V₁₀ and vanadate was compared. V₁₀ increased the surface area of DPPC Langmuir monolayers by 6% and vanadate decreased the surface area by 4%. These results are consistent with V₁₀ interacting with this class of membrane lipids and altering DPPC packing.