The role of Rho GTPases and SNAREs in mediator release from granulocytes

Granulocytes are defined as the population of granulated white blood cells (eosinophils, neutrophils, and basophils). These cells are involved in inflammation and contribute to the pathogenesis of allergic and inflammatory diseases. Inflammation is induced by the release of mediators from granulocytes recruited to or resident within tissues, resulting in edema, leukocyte recruitment, and tissue injury. Eosinophils and neutrophils express Rac1 and Rac2 guanosine triphosphatases (GTPases), 2 members of the Rho GTPase subfamily of ras-related GTPases. Rho GTPases are activated by receptors in the cell membrane and are proposed to function as intracellular molecular switches to regulate mediator release, including exocytosis, from granulocytes. Exocytosis involves granule fusion, which requires the binding of intracellular membrane receptors known as SNAP receptor (SNAREs; soluble N-ethylmaleimide-sensitive factor [NSF] attachment protein [SNAP] receptors). Eosinophils and neutrophils express similar SNARE isoforms that are important in granule fusion events. Together, these molecules link together to form a common signaling pathway for mediator release from granulocytes. Identifying these molecules and their function may provide novel targets for the prevention of inflammatory reactions.