ИСТИНА

Background: Abandoning the fluid-mosaic model of the plasma membrane for the compartmentalized model caused a reconsideration of receptor-ligand interactions. In terms of the new concept, the cortical actin cytoskeleton forms a strong matrix that confines the migration of membrane proteins. Accordingly, low doses of an actin-depolymerizing drug, cytochalasin B (CB), should facilitate phagocytosis of human neutrophils and concomitant granule exocytosis, while high doses should suppress actin remodeling and inhibit phagocytosis and granule exocytosis. We tested our hypothesis in studies concerning the degranulation of neutrophils incubated with CB and stimulated with opsonized zymosan (OZ). Methods: Human neutrophils were isolated from healthy donors by standard density separation. ROS production was measured by the luminol-enhanced chemiluminescence method. Granule exocytosis was determined with flow cytometry, while phagocytosis was tested using imunofluorescence microscopy. Results: Incubation of neutrophils with low doses of CB in combination with OZ led to the stimulation of azurophilic and specific granule exocytosis, while high doses of CB decreased it in a dose-dependent manner, in contrast to the OZ-induced effect. A low dose of CB promoted OZ-induced phagocytosis, while high concentration of the drug totally blocked it. Conclusions: In accordance with a new concept of membrane organization, low doses of CB partially depolymerized actin cytoskeleton, causing an increase in the lateral motility of FcγRs and their clustering, and therefore, amplifying signaling for phagocytosis/accompanying granule exocytosis.