Immunoreceptor FcRIIA of macrophages and neutrophils is involved in phagocytosis and degradation of pathogens. This receptor recognizes antibodies which coat pathogens in blood serum. After binding of antibodies, the receptor is activated and translocates in the plane of the plasma membrane. It eventually accumulates in membrane regions rich in cholesterol and sphingomyelin named rafts. At the same time, rafts merge into larger structures which accommodate cascade signaling molecules governing phagocytosis of the pathogen.
In the present study we investigated whether experimentally induced clustering of sphingomyelin in the plane of the plasma membrane stimulates cell responses similar to those seen during antibody-dependent receptor activation. To induce local clustering of sphingomyelin, cells were exposed to low concentrations of lysenin,a toxin which specifically binds to molecules of sphingomyelin. We have shown that under the influence of lysenin sphingomyelin forms clusters in which FcRIIA receptor accumulated. Within the sphingomyelin microclusters also receptor signaling molecules, Lyn kinase, Cbl, NTAL, were detected. Both the receptor and signaling molecules were phosphorylated which indicated their activation. The results suggest that an interference with the distribution of sphingomyelin in the cell membrane can induce responses similar to those occurring during pathogen recognition by receptor FcRIIA of human immune cells.