Mechanisms of Eosinophil Degranulation

Eosinophils are highly granulated white blood and tissue cells that play complex roles in the immune system including host protection against helminthic parasites, viruses, fungi, and bacteria. These bone marrow-derived cells cause tissue damage in a range of diseases and disorders, particularly in allergy, asthma, and chronic rhinosinusitis with nasal polyps. Eosinophils are recruited to tissues in response to chemotactic signals, and during inflammation, they release a plethora of mediators, including immunoregulatory cytokines, through multiple pathways involving degranulation, respiratory burst, lipid mediator release, exosome release, and extracellular trap formation. Degranulation from eosinophils has been implicated as a major effector mechanism in airway diseases, particularly late phase asthma responses and in nasal polyps from patients with chronic rhinosinusitis. In degranulation responses, eosinophils release numerous granule proteins by classical exocytosis, compound exocytosis, piecemeal degranulation, and cytolysis, which refers to cell lysis through membrane rupture and cell destruction. Cytolysis can lead to suicidal extracellular trap formation, which is a regulated form of cell death involving the release of extracellular DNA traps and granule proteins. Granule release from eosinophils is dependent on activation of specific and tightly regulated intracellular signaling pathways, including Rac and Rab guanosine triphosphatases, soluble NSF attachment protein (SNAP) receptors (SNAREs), Cdk5 kinase, and actin dynamics. These observations have shown selective and nonredundant roles for signaling in degranulation responses. In this review, we explore findings from the literature on the mechanisms controlling granule-derived mediator release from eosinophils.