Functional Extracellular Eosinophil Granules: A Bomb Caught in a Trap

Abstract

Eosinophils store a wide range of preformed proteins, including cationic proteins and cytokines, within their morphologically unique granules. Recently, we have demonstrated that cell-free eosinophil granules are functional, independent, secretory organelles and that clusters of cell-free granules are commonly found at tissue sites associated with various pathologic conditions. Cytolytic release of intact eosinophil granules produces extracellular organelles that are fully capable of ligand-elicited, active, secretory responses and are hence able to act as ‘cluster bombs' that amplify the differential secretory properties of eosinophils. Herein, we review recent progress in elucidating the molecular mechanisms involved in the cytolytical release of intact cell-free functional eosinophil granules in a process associated with the liberation of eosinophil DNA traps (nets), a known aspect of the innate response recognized in various immune cells and pathological conditions. We also discuss the importance of clusters of cell-free eosinophil granules trapped in eosinophil DNA nets in disease and speculate on their potential role(s) in immunity as well as compare available data on DNA-releasing neutrophils.

Eosinophil ETosis and DNA Traps: a New Look at Eosinophilic Inflammation

“…DNA traps containing intact crystalloid granules and lacking liberated granule proteins are consistent with clinical observations and are potentially an important feature of EETosis because cell-free eosinophil granules remain secretion-competent organelles [77]. Remarkably, eosinophil granules themselves express ligand-binding competent cytokine, chemokine, and eicosanoid receptors on the exterior surface of the phospholipid bilayer membrane [48•, 78].…”

“…EETosis provides short-lived, non-dividing eosinophils a mechanism whereby they might continue to maintain stimulus-dependent secretory functions within eosinophil-enriched organs and tissues even after eosinophil death [77, 83]. DNA traps, providing a larger adhesive surface than the cell itself, are central to encapsulation reactions mounted against non-self agents together with intact granules.…”

“…DNA traps, providing a larger adhesive surface than the cell itself, are central to encapsulation reactions mounted against non-self agents together with intact granules. It would be reasonable for the innate role of eosinophil DNA traps to function as a cordon in the airway and/or intestinal lumen or abscess around the non-phagocytosable parasites or fungal hypae [34, 52, 77]. Moreover, cytolytic ETosis results in the release of granule proteins, cytokines, sticky chromatins, DAMPs, and lipid mediators [84] and contributes to the rheological properties of secretions, the local immune response, sterile inflammation, and tissue damage.…”

Depletion of Neutrophils Exacerbates the Early Inflammatory Immune Response in Lungs of Mice Infected withParacoccidioides brasiliensis

“…Additional studies support the hypothesis that the eosinophil participates in the pathophysiology of PCM through its toxic granule proteins [62–64]. In 2013, Muniz et al [65] stated that the cytoplasmic granules of eosinophils are able to function as “cluster bombs” amplifying the differential secretory properties of these cells, releasing cationic proteins, cytokines, chemokines, and growth factors which could contribute to the persistence of infection, exacerbation of the inflammatory response, and subsequent death of P. brasiliensis -infected neutrophil-depleted mice observed in the present study.…”

Lymphocyte-Based Model Systems for Allergy Research: A Historic Overview

“…Intratracheally administered OVA-pulsed eosinophils, similar to conventional APC, induced activation and polarization of OVA-specific T cells in paratracheal lymph nodes [200]. An additional mechanism might be the release of functionally intact cell-free eosinophilic granules, which are frequently found at tissue sites affected by pathological conditions [201]. …”