Journal
TRAFFIC
Volume 6, Issue 10, Pages 866-879Publisher
WILEY
DOI: 10.1111/j.1600-0854.2005.00322.x
Keywords
CD63; electron tomography; eosinophil secretion; major basic protein; chemokines; PAF; piecemeal degranulation; secretory pathway; vesicular transport
Categories
Funding
- NHLBI NIH HHS [HL70270, R01 HL070270-04, R01 HL070270-03, R01 HL070270-02, R01 HL070270] Funding Source: Medline
- NIAID NIH HHS [AI20241, AI22571, R01 AI020241-21A1, AI33372, R01 AI020241-23, R01 AI033372, R01 AI022571-20, R01 AI020241, R01 AI022571-18, R37 AI020241, R01 AI020241-22, R01 AI022571, R01 AI022571-19] Funding Source: Medline
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Eosinophils, leukocytes involved in allergic, inflammatory and immunoregulatory responses, have a distinct capacity to rapidly secrete preformed granule-stored proteins through piecemeal degranulation (PMD), a secretion process based on vesicular transport of proteins from within granules for extracellular release. Eosinophil-specific granules contain cytokines and cationic proteins, such as major basic protein (MBP). We evaluated structural mechanisms responsible for mobilizing proteins from within eosinophil granules. Human eosinophils stimulated for 30-60 min with eotaxin, regulated on activation, normal, T-cell expressed and secreted (RANTES) or platelet activating factor exhibited ultrastructural features of PMD (e.g. losses of granule contents) and extensive vesiculotubular networks within emptying granules. Brefeldin A inhibited granule emptying and collapsed intragranular vesiculotubular networks. By immunonanogold ultrastructural labelings, CD63, a tetraspanin membrane protein, was localized within granules and on vesicles outside of granules, and mobilization of MBP into vesicles within and extending from granules was demonstrated. Electron tomography with three dimension reconstructions revealed granule internal membranes to constitute an elaborate tubular network able to sequester and relocate granule products upon stimulation. We provide new insights into PMD and identify eosinophil specific granules as organelles whose internal tubulovesicular networks are important for the capacity of eosinophils to secrete, by vesicular transport, their content of preformed and granule-stored cytokines and cationic proteins.
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