Mechanisms of eosinophil secretion: large vesiculotubular carriers mediate transport and release of granule-derived cytokines and other proteins

Melo, Rossana C. N.; Spencer, Lisa A.; Dvorak, Ann M.; Weller, Peter F.

doi:10.1189/jlb.0707503

Cited by 103 publications

(118 citation statements)

References 68 publications

(111 reference statements)

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“…Receptor-mediated specific recruitment of cytokines allows release of mediators in a specific and controlled fashion. Under physiological conditions this selective process of piecemeal degranulation does not result in cell death [10].…”

Section: Introductionmentioning

confidence: 98%

“…As is characteristic for cells of the innate immune system the responses they mount to activation are immediate, as many of the mediators are already preformed in the cell and stored in granules or in granule-derived small transport vesicles [10]. Receptor-mediated specific recruitment of cytokines allows release of mediators in a specific and controlled fashion.…”

Section: Introductionmentioning

confidence: 99%

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Eosinophils: important players in humoral immunity

Berek

2015

Clinical and Experimental Immunology

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Summary Eosinophils perform numerous tasks. They are involved in inflammatory reactions associated with innate immune defence against parasitic infections and are also involved in pathological processes in response to allergens. Recently, however, it has become clear that eosinophils also play crucial non‐inflammatory roles in the generation and maintenance of adaptive immune responses. Eosinophils, being a major source of the plasma cell survival factor APRIL (activation and proliferation‐induced ligand), are essential not only for the long‐term survival of plasma cells in the bone marrow, but also for the maintenance of these cells in the lamina propria which underlies the gut epithelium. At steady state under non‐inflammatory conditions eosinophils are resident cells of the gastrointestinal tract, although only few are present in the major organized lymphoid tissue of the gut – the Peyer's patches (PP). Surprisingly, however, lack of eosinophils abolishes efficient class‐switching of B cells to immunoglobulin (Ig)A in the germinal centres of PP. Thus, eosinophils are required to generate and to maintain mucosal IgA plasma cells, and as a consequence their absence leads to a marked reduction of IgA both in serum and in the gut‐associated lymphoid tissues (GALT). Eosinophils thus have an essential part in long‐term humoral immune protection, as they are crucial for the longevity of antibody‐producing plasma cells in the bone marrow and, in addition, for gut immune homeostasis.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Eosinophils: important players in humoral immunity

Berek

2015

Clinical and Experimental Immunology

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“…For example, by applying this technique, which enables optimal access to membrane microdomains, we identified major basic protein (MBP) and cytokines at large vesicles, termed Eosinophil Sombrero Vesicles (EoSVs), involved in the transport of these proteins from secretory granules to the cell surface (Melo et al 2005a;Melo et al 2008;Melo et al 2005b;Melo et al 2009). …”

Section: Research-article2014mentioning

confidence: 99%

Human Eosinophil Leukocytes Express Protein Disulfide Isomerase in Secretory Granules and Vesicles

Dias

Amaral

Carmo

et al. 2014

J Histochem Cytochem.

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SummaryProtein disulfide isomerase (PDI) has fundamental roles in the oxidative folding of proteins in the endoplasmic reticulum (ER) of eukaryotic cells. The study of this molecule has been attracting considerable attention due to its association with other cell functions and human diseases. In leukocytes, such as neutrophils, PDI is involved with cell adhesion, signaling and inflammation. However, the expression of PDI in other leukocytes, such as eosinophils, important cells in inflammatory, allergic and immunomodulatory responses, remains to be defined. Here we used different approaches to investigate PDI expression within human eosinophils. Western blotting and flow cytometry demonstrated high PDI expression in both unstimulated and CCL11/eotaxin-1-stimulated eosinophils, with similar levels in both conditions. By using an immunogold electron microscopy technique that combines better epitope preservation and secondary Fab-fragments of antibodies linked to 1.4-nm gold particles for optimal access to microdomains, we identified different intracellular sites for PDI. In addition to predictable strong PDI labeling at the nuclear envelope, other unanticipated sites, such as secretory granules, lipid bodies and vesicles, including large transport vesicles (eosinophil sombrero vesicles), were also labeled. Thus, we provide the first identification of PDI in human eosinophils, suggesting that this molecule may have additional/specific functions in these leukocytes. (J Histochem Cytochem 62:450-459, 2014)

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“…Eosinophils secrete a variety of cytokines and chemokines [18]. They have potentials to promote allergic inflammation by producing Th2-type cytokines such as IL-4 [19], IL-13 [20] and IL-9 [9] or to cause airway remodeling by producing TGF-β [21, 22].…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Proteases Activate Eosinophil Function in vitro

Hiraguchi

Nagao²,

Hosoki³

et al. 2008

Int Arch Allergy Immunol

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Background: Recent evidence suggests that both neutrophilic and eosinophilic inflammation persist in the airways of patients with severe asthma. Mechanisms for interaction between neutrophils and eosinophils are still to be understood. Since eosinophils express protease-activated receptor 2, neutrophil-derived serine proteases may activate eosinophils. Objective: We investigated the effect of neutrophil serine proteases on eosinophil effector functions. Methods: Peripheral blood eosinophils were stimulated with elastase, cathepsin G and proteinase 3. Superoxide generation was quantitated with the cytochrome C reduction method. A panel of cytokines and chemokines in the culture supernatants were measured with a multiplex beads array system. Effects of an elastase inhibitor, sivelestat, and a serine protease inhibitor, PMSF, on the protease-induced reactions were also tested. Results: Neutrophil proteases significantly induced superoxide production from eosinophils. Elastase was the most potent among them. Sivelestat and PMSF inhibited the reaction. The proteases induced production of IL-6, IL-8, TNF-α and GRO-α, that have a possible connection with neutrophilic inflammation. Conclusion: Neutrophil proteases activate eosinophils to produce superoxide, proinflammatory cytokines and neutrophilotactic chemokines and may further aggravate airway inflammation in patients with severe asthma.

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Mechanisms of eosinophil secretion: large vesiculotubular carriers mediate transport and release of granule-derived cytokines and other proteins

Cited by 103 publications

References 68 publications

Eosinophils: important players in humoral immunity

Eosinophils: important players in humoral immunity

Human Eosinophil Leukocytes Express Protein Disulfide Isomerase in Secretory Granules and Vesicles

Neutrophil Proteases Activate Eosinophil Function in vitro

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